Measurement of susceptibility to diabetic foot ulcers

Abstract

A device and method for measuring capacitance as an indicator of susceptibility to diabetic foot ulcer formation is provided. [Solution] The device includes a plurality of electrodes embedded in a substrate, where a pair of the electrodes can form a capacitance sensor configured to measure a first capacitance of a first region of tissue adjacent 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 instructions stored on the non-transitory computer-readable medium.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority of U.S. Provisional Application No. 62 / 454,482, filed on February 3, 2017, and U.S. Provisional Application No. 62 / 521,917, filed on June 19, 2017, each of which is hereby incorporated by reference in its entirety.

[0002] The present disclosure provides an apparatus and method for evaluating the feet of patients at risk of developing diabetic foot ulcers.

Background Art

[0003] Diabetic foot ulcers are the cause of more hospitalizations than any other complication of diabetes. Non - enzymatic glycation induced by elevated blood sugar levels causes ligaments to harden and an increase in cross - links in collagen. These conditions can lead to damage to cell walls and blood vessels, resulting in an initial increase in the amount of extracellular fluid (ECF). Peripheral neuropathy causes loss of protective sensation and loss of coordination of muscle groups in the feet and legs. Neuropathy can cause an increase in mechanical stress on the foot during walking, and, combined with the tissue weakening induced by diabetes, if the stress is not reduced by withstanding the stress, it will progress to tissue death. Neuropathy also reduces the patient's ability to perceive pain normally associated with stress and tissue damage, allowing the condition to progress.

[0004] Each year, approximately 5% of diabetic patients develop foot ulcers, and 1% will require amputation of a toe or some part of the foot. In the long term, 15% of patients with diabetes will develop foot ulcers, 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 treatment is related to the treatment and healing of foot ulcers after they occur.

[0005] Current approaches to preventing diabetic foot ulcers include patient education, foot and toenail care, appropriate footwear selection, and prophylactic surgical intervention. Detecting pre-ulcer conditions can enable the implementation of preventive techniques such as reducing stress and improving hygiene. [Overview of the project]

[0006] In one embodiment, the present disclosure provides and includes an apparatus for evaluating the susceptibility of tissue to the formation of diabetic foot ulcers, the apparatus comprising: a plurality of electrodes embedded in a substrate, wherein a pair of electrodes can form a capacitance sensor, which is a capacitance sensor configured to measure a first capacitance of a first area of ​​tissue adjacent to the capacitance sensor; a circuit electrically coupled to the electrodes; a processor electrically coupled to the circuit; and a non-temporary computer-readable medium electrically coupled to the processor and including instructions stored in the non-temporary computer-readable medium, which performs the steps of: receiving information from the circuit regarding a first capacitance measured from the capacitance sensor when the instructions are executed on the processor; 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 exceeding a first predetermined threshold.

[0007] In one embodiment, the present disclosure provides and includes a method for evaluating the susceptibility of tissue to the formation of diabetic foot ulcers, the method comprising: obtaining a first capacitance value at a first location on the 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 diabetic foot ulcers when the first capacitance value differs from a first reference value by an amount exceeding a first predetermined threshold, and the temperature measurement differs from a second reference value by an amount exceeding a second predetermined threshold.

[0008] In some embodiments, the present disclosure provides and includes a method for evaluating the susceptibility of tissue to the formation of diabetic foot ulcers, the method comprising: obtaining a first subepidermal moisture (SEM) value at a first location on the 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 diabetic foot ulcers when the first SEM value differs from a first reference value by an amount exceeding a first predetermined threshold, and the temperature measurement differs from a second reference value by an amount exceeding a second predetermined threshold.

[0009] In one embodiment, the present disclosure provides 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, each of which is configured to measure subcutaneous moisture (SEM) levels at different 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 the SEM measurement period; and the external controller controlling the two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

[0010] In one embodiment, the present disclosure provides 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 arranged on a flexible substrate such that the current passing between the electrodes passes through tissue in close proximity to the location of the patient's skin, and an external controller electrically connected to the two electrodes. [Brief explanation of the drawing]

[0011] Aspects of the present disclosure are described herein merely as examples, with reference to the accompanying drawings. The drawings will now be referenced in detail, but it is emphasized that the items shown are illustrative and intended for illustrative purposes of the aspects of the present disclosure. In this regard, the description and drawings, either individually or together, will make it clear to those skilled in the art how aspects of the present disclosure may be carried out.

[0012] [Figure 1A] Describe the structure of the foot. [Figure 1B] This is an enlarged view of area A in Figure 1A. [Figure 2A] This depicts an early open ulcer at time 0. [Figure 2B] The pressure profile created in the state shown in Figure 2A is depicted. [Figure 2C] This depicts the same region of tissue in Figure 2A at time point 1. [Figure 2D] Figures 2A and 2C depict the same tissue regions at time point 2. [Figure 3A] A toroidal bioimpedance sensor is disclosed. [Figure 3B] The idealized electric field map generated by the toroidal sensor shown in Figure 3A at startup is disclosed. [Figure 3C] A SEM scanner equipped with the sensor shown in Figure 3A is disclosed. [Figure 4] This is a first exemplary electrode array. [Figure 5] This is an exemplary electrode array according to the present disclosure. [Figure 6A] Figure 5 illustrates a first example of how the electrode array disclosed in this disclosure is configured to form a bioimpedance sensor. [Figure 6B] Figure 5 illustrates a first example of how the electrode array disclosed in this disclosure is configured to form a bioimpedance sensor. [Figure 6C] An example of a first sensor formed by an array of electrodes according to this disclosure is illustrated. [Figure 6D] This disclosure illustrates an example of how the second sensor is formed and how it overlaps with the first sensor in Figure 6C. [Figure 6E] This disclosure illustrates how the sensor shown in Figure 6A is formed from an array of electrodes larger than the portion of the patient's skin in which the array is positioned. [Figure 6F]Illustrates the positions of the left and right feet for SEM measurement according to the present disclosure. [Figure 6G] A plot of SEM values associated with known relative locations for identifying symmetric locations according to the present disclosure. [Figure 7A] Depicts a first example of a mat assembly incorporating a plurality of bioimpedance sensors according to the present disclosure. [Figure 7B] Depicts a second example of a mat assembly comprising an array of electrical sensors according to the present disclosure, disposed such that while standing on the mat assembly, they are respectively under the left and right feet of the patient. [Figure 7C] Depicts a third example of a mat assembly comprising one or more sensors disposed within each of the contours according to the present disclosure. [Figure 8A] Discloses a foot cover incorporating a bioimpedance sensor according to the present disclosure. [Figure 8B] A cross-sectional view of the foot cover of FIG. 8A showing the location of the bioimpedance sensor according to the present disclosure. [Figure 9] Discloses a sandal incorporating a bioimpedance sensor according to the present disclosure. [Figure 10A] Depicts a first exemplary configuration of an addressable electrode of FIG. 5 for varying the performance of the sensor according to the present disclosure. [Figure 10B] Depicts a second exemplary configuration of an addressable electrode of FIG. 5 for varying the performance of the sensor according to the present disclosure. [Figure 10C] Depicts a third exemplary configuration of an addressable electrode of FIG. 5 for varying the performance of the sensor according to the present disclosure. [[ID=3,2]]<00,00105> Shows an exemplary configuration of a substrate shaped to be positioned at a known location on the skin of a patient according to the present disclosure. [Figure 11B] Shows a front view of the exemplary configuration of FIG. 11A according to the present disclosure. [Figure 12] Depicts a schematic diagram of an integrated system for measuring, evaluating, storing, and transmitting SEM values according to the present disclosure. [Figure 13]This disclosure describes the sensing band. [Figure 14A] This disclosure describes an integrated sensor and stimulator assembly suitable for the treatment of pressure ulcers. [Figure 14B] This disclosure describes an integrated sensor and stimulator assembly suitable for the treatment of pressure ulcers. [Figure 14C] This disclosure describes an integrated sensor and stimulator assembly suitable for the treatment of pressure ulcers. [Figure 14D] This disclosure describes a bandage assembly suitable for the treatment of pressure ulcers. [Figure 15A] An exemplary method for performing a SEM measurement starting at the posterior heel, in accordance with this disclosure, is illustrated. [Figure 15B] An exemplary method for performing a SEM measurement starting at the lateral heel, in accordance with this disclosure, is illustrated. [Figure 15C] An exemplary method for performing a SEM measurement starting at the medial heel, in accordance with this disclosure, is illustrated. [Modes for carrying out the invention]

[0013] This disclosure describes the measurement of various electrical characteristics and the derivation of SEM values ​​indicating an increase in the amount of ECF, as well as the application of this information to the assessment of diabetic foot ulcers and their susceptibility to treatment.

[0014] Diabetic foot ulcers are known to occur in areas exposed to repetitive, moderate stress, particularly in the bony parts of the foot that shift weight onto adjacent tissues while standing. Because the damage can initially occur in the tissue beneath the skin, it may not be detectable by visual inspection. Early damage will release fluid into the extracellular space, which can be detected through the electrical properties of the subepidermal tissue, such as measuring the tissue's capacitance. Monitoring of the ECF in potentially high-risk areas will detect tissue deterioration that, if left undetected, will progress to open ulcers.

[0015] This description is not intended to be a detailed enumeration of all different ways in which the Disclosure may be carried out, or all features that may be added to the Disclosure. For example, a feature illustrated in one embodiment may be incorporated into another embodiment, and a feature illustrated in a particular embodiment may be omitted from that embodiment. Thus, the Disclosure is intended to show that in some embodiments of the Disclosure, any feature or combination of features described herein may be excluded or omitted. Furthermore, numerous variations and additions to the various embodiments proposed herein will be apparent to those skilled in the art in light of the Disclosure and will not deviate from the Disclosure. In other examples, well-known structures, interfaces, and processes are not shown in detail so as not to unnecessarily obscure the invention. Nothing in this specification is intended to be construed as negating any part of the entire scope of the Invention. For this reason, the following description is intended to illustrate some specific embodiments of the Disclosure and not to exhaustively identify all substitutions, combinations, and variations thereof.

[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs. Technical terms used in describing the disclosure herein are for the purpose of describing specific aspects or embodiments only and are not intended to limit the disclosure.

[0017] All publications, patent applications, patents, and other references cited herein are incorporated by reference in their entirety with respect to the teachings relating to the texts and / or paragraphs in which the references are presented. References to the art used herein are intended to refer to art that is generally understood in the art, including variations or substitutions of equivalent art to those art, which would be obvious to those skilled in the art.

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

[0019] U.S. Patent Application No. 15 / 134,110 discloses an apparatus for measuring subcutaneous water (SEM) similar to the device shown in Figure 3C, wherein the device emits and receives an RF signal at a frequency of 32 kHz through a single coaxial sensor, produces a bioimpedance signal, and then converts this signal into an SEM value.

[0020] Both U.S. Patent Applications No. 14 / 827,375 and No. 15 / 134,110 are incorporated herein by reference in their entirety.

[0021] Unless otherwise indicated, it is expressly intended that the various features of this disclosure described herein may be used in any combination. Furthermore, in some embodiments of this disclosure, it is also intended that 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 methods. The steps and / or actions of the methods are interchangeable with one another without departing from the scope of the invention. In other words, unless a specific order of steps or actions is required for the correct operation of the embodiments, the specific order and / or use of steps and / or actions may be modified without departing from the scope of the invention.

[0023] Where used in this disclosure and the accompanying claims, the singular forms "a," "an," and "the" are intended to include the plural forms similarly unless otherwise clearly indicated.

[0024] As used herein, "and / or" means and encompasses any and all possible combinations of one or more of the enumerated items relating to each other, as well as the absence of any combination when interpreted otherwise ("or").

[0025] The terms “about” and “approximately,” as used herein when referring to measurable values ​​such as length, frequency, or SEM values, mean to include variations of a particular quantity of ±20%, ±10%, ±5%, ±1%, ±0.5%, or even ±0.1%.

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

[0027] As used herein, the terms “subcutaneous fluid” or “SEM” refer to local edema caused by an increase in tissue fluid and other changes that alter the underlying structure of damaged tissue in the presence of vascular leakage and continuous pressure on the tissue, apoptosis, necrosis, and inflammatory processes.

[0028] As used herein, “system” may be a collection of devices that are wired or wirelessly connected to one another.

[0029] As used herein, “examine” refers to the use of radiofrequency energy that penetrates the patient’s skin.

[0030] As used herein, “patient” may refer to a person or an animal.

[0031] As used herein, “healthy” may describe tissue that does not show signs of damage to the cell wall or blood vessels, where the presence of an increase in ECF is an indicator of such damage.

[0032] As used herein, “extracellular fluid” or “ECF” refers to the fluids contained outside cells, including plasma, interstitial fluid, and interstitial fluid.

[0033] As used herein, "susceptible to the formation of diabetic foot ulcers" may describe tissue that shows symptoms of damage to the cell wall or blood vessels, such as edema or increased ECF, but in which open ulcers are not present.

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

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

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

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

[0038] Figure 1B is a magnified view of area "A" in Figure 1A. The ends of the metatarsal bones 22 and adjacent phalanges 23 are shown in close proximity to the skin 24 on the sole of the foot 20. A portion of the patient's weight creates a compressive force 30 applied by the metatarsal bones 22 to the tissue within area 40. Force 30 is counteracted by a resistive force 36 applied by the floor to the skin 24 beneath area 40 to support the patient. Muscle activity by the patient walking on their feet or simply balancing while standing creates a shear force 32 between the metatarsal bones 22 and the tissue 40, as well as a resistive shear force 38 between the floor and the skin 24. Thus, the tissue within area 40 is simultaneously subjected to both compressive and shear forces.

[0039] Healthy patients are observed to shift their weight from foot to foot while standing still, as well as shift the center of mass relative to their feet. This limits the duration for which force is applied to any particular area of ​​tissue. However, peripheral neuropathy reduces sensation within the tissue created by the patient's weight, and therefore reduces the unconscious shift of the patient's weight. Patients with peripheral neuropathy are observed to lack normal movement while standing. This leads to prolonged periods of continuous compressive force applied to local areas of tissue, such as region 40. It is thought that prolonged exposure to moderate levels of force in this way is the cause of ulcer formation in these areas.

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

[0041] Figure 2B shows the pressure profile created in the state of Figure 2A. The force applied by the floor or by the shoes worn by the patient is applied as a locally uniform pressure 56 to the skin 24 of the foot 20. The applied pressure 56 is counteracted internally by a force 53. When the tissue is detached, it is no longer possible to apply pressure over the ulcer 50. Thus, the internal force in the toroidal region 52A increases to a peak 54, obtaining the force that would have been applied to the ulcer 50. This peak force 54 is high enough to cause further tissue damage in the ring 52A. As the body attempts to protect itself from the increased pressure, a callus will generally form over the region 52A. However, the tissue beneath the callus is still damaged and will show an increase in ECF.

[0042] Figure 2C depicts the same region of tissue at time 1 following time 0. The increase in pressure level in region 52A leads to tissue death in region 52A, causing the tissue in region 52 to peel off, and thus the ulcer 50B becomes larger than the previous ulcer 50A. The applied pressure 56 remains unchanged, therefore the tissue in region 52B around the larger ulcer 50B needs to experience an even greater force. This accelerates the expansion of the ulcer 50, as the tissue in region 52B dies more rapidly under a greater applied load.

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

[0044] In the situation shown in Figure 2A, where an ulcer has formed, interventional treatment would be introduced to prevent the ulcer from growing and to allow the body to heal the open ulcer. Treatment may involve placing pressure-relieving pads around the ulcer to diffuse the pressure over a larger area of ​​healthy tissue and eliminate the peaks that would cause further damage. However, determining whether the treatment is working is only possible through time-series observation that the ulcer is not progressing.

[0045] Figure 3A discloses a toroidal bioimpedance sensor 90. In this exemplary configuration, a central electrode 110 is surrounded by a ring electrode 120. Although not limited to any particular theory, the gap between the two electrodes affects the depth to which the electric field penetrates the substrate beneath the sensor 90. In one embodiment, a grounding plate (not visible in Figure 3A) is parallel to and away from the electrode surfaces, and in some embodiments, extends beyond the outer diameter of the ring electrode 120. Although not limited to any particular theory, the grounding plate may restrict the electric field between electrodes 110 and 120 to a single side of the electrode surfaces 110 and 120 that is opposite the grounding plate from the surfaces of electrodes 110 and 120.

[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, extending outward from the surfaces of electrodes 110 and 120 to a depth of electric field 150. The diameter of the central electrode 110, the inner and outer diameters of the ring electrode 120, and the gap between electrodes 110 and 120 can be varied to alter the characteristics of the electric field 140, for example, the depth of the electric field 150.

[0047] During use, the drive circuit can measure electrical characteristics or parameters, including one or more electrical features selected from the group consisting of resistance, capacitance, inductance, impedance, magnetoresistance, and other electrical features such as those sensed by the electric field 140. Depending on the type of drive circuit used in the device, the device's sensors may be bipolar radio frequency sensors, bioimpedance sensors, capacitance sensors, or SEM sensors. In one embodiment, the measured electrical parameters relate to the moisture content of the patient's epidermis at a depth determined by the arrangement of electrodes 110 and 120, the frequency and intensity of the electric field 140, and other operating characteristics of the device's drive circuit. In one embodiment, the measured moisture content is equivalent to an SEM content having a certain value on a predetermined scale. In one embodiment, a predetermined scale may be in the range of 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, a predetermined scale may be determined by one or more factors based on the values ​​provided herein. In one embodiment, multiple measurements are performed while varying one or more of these operational characteristics during the reading, thereby providing information relating to the water content at various depths of the skin.

[0048] One or more regions can be defined on the body. In some embodiments, measurements made within a region are considered comparable to one another. A region can be defined as an area on the skin of the body where measurements can 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 can be defined as a set of two or more specific points relating to an anatomical feature where measurements are taken only at specific points. In some embodiments, a region can comprise multiple discontinuous areas on the body. In some embodiments, a set of specific locations can comprise points within multiple discontinuous areas.

[0049] In one embodiment, the region is defined by a surface area. In another embodiment, the region is, for example, 5 to 200 cm². 2 5-100cm 2 , 5-50cm 2 , or 10-50cm 2 , 10-25cm 2 , or 5-25cm 2 It is possible.

[0050] In some embodiments, measurements may be made in a specific pattern or a portion thereof. In some embodiments, the reading pattern is made in a pattern that includes a central target area. In some embodiments, measurements are made in one or more circular patterns of increasing or decreasing size, T-shaped patterns, sets of specific locations, or randomly across tissue or regions. In some embodiments, the pattern may be positioned on the body by defining a first measurement location of the pattern relating to an anatomical feature, including the remaining measurement locations of the pattern defined as offsets from the first measurement location.

[0051] In one embodiment, multiple measurements are taken across a tissue or region, and the difference between the lowest and highest measurements is recorded as the delta value of those measurements. In another embodiment, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more measurements are taken across a tissue or region.

[0052] In some embodiments, a threshold may be established for at least one region. In some embodiments, thresholds of 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or other values ​​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 satisfy or exceed the threshold associated with that region. In some embodiments, each of multiple regions has a different threshold. In some embodiments, two or more regions may have a common threshold.

[0053] In one embodiment, the threshold has both a delta value component and a time-series component, where the delta value is identified as significant when it exceeds a predetermined value for a given portion of the time interval. In one embodiment, the given portion of the time interval is defined as the minimum of X days in which multiple measurements taken on that day produce a delta value greater than or equal to a predetermined value within a total of Y consecutive days of measurements. In one embodiment, the given portion of the time interval may be defined as 1, 2, 3, 4, or 5 consecutive days in which multiple measurements taken on that day produce a delta value greater than or equal to a predetermined value. In one embodiment, the given portion of the time interval may be defined as a portion of a different specific period (week, month, hour, etc.).

[0054] In one embodiment, the threshold has a trend mode in which the changes in delta values ​​of a series of measurements are compared with one another. In one embodiment, the trend threshold is defined as a predetermined change in delta value over a predetermined length of time, where the determination that the threshold is met or exceeded is significant. In one embodiment, a determination of significance will trigger a warning. In one embodiment, a trend line can be calculated from a portion of the individual measurements of a series of measurements. In one embodiment, a trend line can be calculated from a portion of the delta values ​​of a series of measurements.

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

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

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

[0058] In one embodiment, the measured value, for example, the threshold value, is determined by a SEM scanner model 200 (Bruin Biometrics, LLC, Los Angeles, CA). In another embodiment, the measured value is determined by a different SEM scanner.

[0059] In some embodiments, the measurements are based on capacitance measurements obtained by referencing a reference device. In some embodiments, the capacitance measurements may depend on the location of any electrode in the device and, in other embodiments, on the case. Such variations may be compared to reference SEM devices such as the 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 match the differential capacitance range obtained by referencing a reference device.

[0060] Figure 3C provides top and bottom views of an SEM scanner 170, which includes electronic equipment that drives a sensor 174 similar to the sensor 90 in Figure 3A to measure the capacitance between electrodes 110 and 120. This capacitance can be converted into an SEM value displayed on a display device 176.

[0061] Embodiments of the sensor 90 and the SEM scanner 170 are disclosed in U.S. Patent Application No. 15 / 134,110, filed in national phase entry, WO2016 / 172263, all of which are incorporated herein by reference in their entirety.

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

[0063] Any pair of electrodes, whether consisting of a single electrode or a set of electrodes coupled together to form a virtual electrode, is coupled to an electronic device (not shown in Figure 4) configured to measure an electrical characteristic or parameter, including resistance, capacitance, inductance, impedance, magnetoresistance, or one or more of the sensors 90, 174, 290, 430, 440, or other electrical features, including other two-electrode sensors. The electronic device of this 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 an amount exceeding a threshold. In some embodiments, one or both of the reference value and the threshold are predetermined.

[0064] Figure 5 depicts another exemplary array 400 of electrodes 410 according to this disclosure. In this non-limiting example, each electrode 410 is substantially 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 one embodiment, the gap 420 is uniform among all electrodes 410. In one embodiment, the gap 420 differs among the various electrodes. In one embodiment, the gap 420 is narrower than the cross-section of each electrode 410. The electrodes 410 can be interconnected to form a virtual sensor as described below with respect to Figures 6A-6B and 10A-10C.

[0065] Figure 6A depicts an array 400 of electrodes 410 connected to, for example, a measuring circuit, configured to form an exemplary sensor 430 according to the present disclosure. A single hexagonal electrode 410 labeled "1" forms the central electrode, and a ring of electrodes 410 labeled "2" are interconnected to form a ring electrode. In one embodiment, the electrodes 410 between the central electrode and the ring electrode are electrically "floating". In one embodiment, the electrodes 410 between the central electrode and the ring electrode are grounded or connected to floating ground. In one embodiment, 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 floating ground.

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

[0067] Figures 6A and 6B depict exemplary configurations of an electrode array 400 that can form sensors 430 at multiple overlapping locations according to the present disclosure. In Figure 6A, the virtual sensor 430A is formed by a central electrode 432 formed by a single electrode 410 indicated as “1”, and a ring electrode 434 formed by multiple electrodes 410 indicated as “2”. This same array 400 is shown in Figure 6B, where a new virtual sensor 430B is formed by a central electrode 436 indicated as “3”, and a ring electrode 438 indicated as “4”. The location of the virtual sensor 430A is indicated by a black outline. It can be seen that the virtual sensor 430B overlaps with the location of the virtual sensor 430A, which makes it possible to produce measurements with a resolution finer than the diameter of the sensor 430.

[0068] Figure 6E illustrates a method according to this disclosure in which a sensor 430 may be formed from an array of electrodes 400 that are larger than a portion of the patient's skin positioned relative to the array. In this example, the contour of the contact area 450 on the sole 22R of the patient's right foot, as viewed from directly below the foot, is shown superimposed on the array 400. In this example, the sensor 430C is formed where a portion of the sensor 430C extends beyond the edge of the contact area 450. At such a location, the capacitance or other electrical parameters measured by the sensor 430C are lower than the capacitance measured by the sensor 430D which is fully positioned within the contact area 450. It can be seen that the sensor 430 may be formed at any point within the array 400 and may partially overlap the contact area at any level within the range of 0 to 100%, depending on the position of the sensor 430.

[0069] In one embodiment, the 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 another embodiment, the 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 embodiment, the sensor array 400 may further comprise a plurality of contact sensors (not shown in Figure 6E) on and surrounding each of the electrodes, on the same flat surface as each of the electrodes, to ensure complete contact of one or more virtual sensors to the skin surface. The plurality of contact sensors may be a plurality of pressure sensors, a plurality of light sensors, a plurality of temperature sensors, a plurality of pH sensors, a plurality of sweat sensors, a plurality of ultrasonic sensors, a plurality of bone growth stimulator sensors, or a plurality of combinations thereof. In some embodiments, the plurality of contact sensors may comprise four, five, six, seven, eight, nine, or ten or more contact sensors surrounding each electrode.

[0071] Figures 6F and 6G illustrate an example of how, according to this disclosure, comparing SEM values ​​associated with sensors at known relevant locations may identify symmetrical locations. In this example, sensors 430 are formed at non-overlapping locations, spanning the contact area 450R of the right foot 20R, marked “A” through “H” in Figure 6F. The SEM values ​​measured at each location are plotted in the graph of Figure 6G. In this example, the SEM values ​​at locations “A” and “H” are low or zero, reflecting the non-overlapping sensors 430 including the contact area 450 at these locations. The SEM values ​​associated with locations “B” and “G” are higher because sensors 430 overlap with portions of the contact area 450 at these locations. The SEM values ​​for locations C, D, E, and F are higher and, in this example, nearly the same, indicating that sensors 430 are entirely within the contact area 450 at these locations. In one embodiment, an SEM measuring device such as apparatus 180 may determine that certain locations, for example, locations "C" and "F", are symmetrical with respect to the center line 452R of the right foot 20R. In one embodiment, where a similar set of measurements is produced at locations A' to H' on the left foot 20L, locations on each foot 20L and 20R, for example, locations E and E', may be determined to be approximately symmetrical.

[0072] Figure 7A depicts an exemplary mat assembly 500 incorporating a plurality of bioimpedance sensors 520 according to the present disclosure. Although the sensors 520 are shown as toroidal sensors similar to the sensor 90 depicted in Figure 3A, the sensors 520 may be any configuration of an electrical measuring sensor, including the configurations shown in Figures 4, 5, and 6A-6B. The sensors 520 are distributed across a substrate 510. In one embodiment, a portion of the substrate 510 is flexible. In one embodiment, a portion of the substrate 510 is rigid. In one embodiment, the electrodes of the sensors 520 are electrically bare, thereby allowing conductive electrical contact with the 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 Figure 7A), thereby allowing only capacitive electrical contact with the patient's feet when the patient is standing on the mat assembly 500.

[0073] In one embodiment, the mat assembly 500 includes one or more temperature sensors (not shown in Figure 7A) that detect the temperature of one or more locations on the feet. In one embodiment, the temperature sensors are installed together with a SEM sensor 520 to provide temperature and SEM measurements for a common location.

[0074] In one embodiment of the mat assembly 500, a signal is provided when the measured capacitance differs from a reference capacitance value by an amount exceeding a first threshold, and the measured temperature differs from a temperature reference value by an amount exceeding a second threshold. In one embodiment, one or both of the thresholds are predetermined. In one embodiment, the first threshold is set to the corresponding reference capacitance value + 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 the corresponding reference temperature value + 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, one or both of the capacitance and temperature reference values ​​are determined from a rolling average of the last five sequential measurements, by averaging the previous measurements, e.g., multiple measurements made over an earlier period, e.g., one month ago.

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

[0076] Figure 7B depicts another exemplary mat assembly 502, which includes arrays 530L and 530R of electrical sensors 520, where arrays 530L and 530R are positioned under the left and right feet, respectively, of the patient while standing on the mat assembly 502. In one embodiment, the contours 540L and 540R of the left and right feet are drawn across arrays 530L and 530R to guide the patient to stand in the correct position.

[0077] Figure 7C illustrates 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 positioned in a location corresponding to the part of the foot most likely to develop ulcers, for example, the ball of the foot. In one embodiment, sensor 520B may be positioned under the heel or other part of the foot.

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

[0079] Regular use by patients of mat assemblies 500, 502, 504, etc., can serve the function of detecting changes in the patient's foot health. For example, at the time of a clinician's examination to verify that there are no indicators of ulcers or injuries that would lead to ulcer formation in the patient, a baseline will be established by measuring electrical characteristics such as capacitance of each foot. The patient then places the mats 500, 502, 504 in an easily accessible location in the patient's home, for example, in front of the bathroom sink. Regularly, such as while brushing teeth daily, the patient triggers a measurement of their feet by the sensor 520. If the patient is standing in the same place, for example, guided by contours 540L and 540R, each sensor 520 and 550 is measuring the same position for each repeated measurement. In one embodiment, temperature measurements are made in the mat assemblies 500, 502, 504 by an infrared sensor 550 or one or more temperature sensors (not shown in Figure 7C). In one embodiment, images are captured in the mat assembly 504 by an optical sensor 550. This information is stored in local memory or transmitted to a remote memory location, such as a doctor's office. Each daily measurement is compared to a baseline value derived from previous measurements, e.g., measurements made in the clinician's office, or the average of the previous week's measurements. If the latest measurement deviates from the baseline value, the patient is informed of the deviation. The patient can then seek advice from the clinician regarding further evaluation and possible actions. In one embodiment, a change in measured SEM value greater than a threshold triggers a notification. In another embodiment, both a change in measured SEM value greater than a first threshold and a change in measured temperature greater than a second threshold trigger a notification. In yet another embodiment, either a change in measured SEM value greater than a first threshold or a change in measured temperature greater than a second threshold triggers a notification.In one embodiment, the first threshold is set to the corresponding reference SEM value + 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 the corresponding reference temperature 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, information such as images of the soles of the patient's feet is always sent to the clinician for review.

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

[0081] Figure 8A discloses a foot cover 600 incorporating a bioimpedance sensor 520 as shown in the cross-sectional view of Figure 8B, according to this disclosure. In one embodiment, the foot cover 600 comprises a sock or other flexible, form-fitting garment 610 into which a 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 conventional shoe, such as a leather shoe or a sneaker. The sensor 520 is placed in one or more locations corresponding to the area 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 underside of the flexible, form-fitting garment 610. In one embodiment, the sensor 520 is placed in the area around the toes (not visible in Figure 8B) of the flexible, form-fitting garment 610.

[0082] Figure 9 discloses a sandal 650 incorporating a bioimpedance sensor 520 according to the present disclosure. One or more sensors 520 are positioned on the sandal at locations corresponding to areas of potential ulcer development.

[0083] Figures 10A, 10B, and 10C illustrate the addressable electrode configurations of Figure 5 that vary the performance of the sensor according to this disclosure. Figure 10A illustrates an exemplary first configuration 700 in which electrodes 710 are connected to form a central electrode 720 and a ring electrode 730 similar to the electrodes in Figures 6A and 6B. Referring to Figure 3B, the sensor configuration 700 has gaps 740 between a single row of electrodes 710 that produce a first electric field depth 150.

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

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

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

[0087] Figures 11A and 11B depict exemplary embodiments of a sensor assembly 500 configured to be positioned at known locations on a patient's skin, according to the present disclosure. In this embodiment, the sensor assembly 500 has a molded substrate 510 configured to fit snugly to the rear and bottom surface of the heel portion of a foot 20. In one embodiment, the molded substrate 510 is suitable for use with both a left foot 20L and a right foot 20R. The sensor assembly 500 comprises one or more sensors 520 disposed on the inner surface of the molded substrate 510. In this embodiment, the sensor 520 is configured as a toroidal sensor, as shown in Figure 1A. In one embodiment, the inner surface of the molded substrate 510 is aligned with an array 400 of electrodes 410, referring to Figure 5, so that a virtual sensor can be formed at any location. In one embodiment, sensors of other shapes and configurations are provided on the inner surface of the molded substrate 510. In one embodiment, the molded substrate 510 is a flexible panel (not shown in Figure 11A) that can be fitted tightly 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 circuits, processors, communication subsystems, or other types of electronic assemblies (not shown in Figure 11A) configured to measure one or more of a power supply, capacitance, or other electrical properties.

[0088] Figure 11B depicts an exemplary configuration of the sensor assembly 500 in which multiple sensors 520 are arranged on a molded substrate 510, for example, when the sensor assembly 500 is positioned against the patient's skin around the posterior, lateral, and sole of the center of the right heel. This makes it possible to perform multiple SEM measurements at repeatable locations on the heel with the sensor assembly 500 in a single position. In one embodiment (not shown in Figures 11A and 11B), the sensor assembly 500 is configured to be positioned on a portion of the patient's posterior, thus providing the ability to produce measurements at symmetrical locations on the posterior. In one embodiment, the molded substrate 510 is configured to conform to the anatomical features of the patient's target area. In one embodiment, the molded substrate 510 includes marks or other indicators that may conform to the patient's body features to allow 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 the lining of clothing or shoes or other garments. In one embodiment, the sensor assembly 500 is integrated into a sheet, blanket, liner, or other type of bedding. In one embodiment, the sensor assembly 500 has wireless communication capabilities, such as passive radio frequency identification (RFID) or inductive coupling, which enable the operation of the sensor 520 without a physical connection to the sensor assembly 500.

[0089] In one embodiment, the sensor 520 is coupled to electronic equipment (not shown in Figure 11B) configured to compare the current set of measurements with each other and with past measurements made at the same location. In one embodiment, the electronic equipment of the Disclosure may provide a signal if 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 with the difference between measurements made at the same two locations at a previous point in time, and a change in a value measured at a particular location from a previous measurement at the same location that exceeds a threshold amount.

[0090] Figure 12 depicts a schematic diagram of an integrated system 800 for measuring, evaluating, storing, and transmitting SEM values ​​according to this disclosure. In this example, system 800 comprises a SEM measurement device 810, e.g., a SEM scanner 170, which includes the ability to wirelessly communicate with a WiFi access point 820. The device 810 communicates with one or more of the following: an SEM application running on a server 850, a laptop computer 840, a "smartphone" 830, or an application running on another digital device. In some embodiments, the laptop computer 840 and the smartphone 830 are carried by a user of the device 810, e.g., a nurse, and the application provides feedback and information to the user. In some embodiments, patient information received from the device 180 is stored in a database 850. In one embodiment, patient information received from the device 810 is stored in a database 860. In one embodiment, information received from device 810 is transferred via network 855 to another server 880 that stores a portion of the information in the patient's electronic medical record (EMR) 870. In another embodiment, information retrieved from device 810 or 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 doctor's office treating the patient.

[0091] In one embodiment, the device 810 is one of a mat assembly 500, a foot cover 600, or another measuring device, and the patient uses either or both a smartphone 830 and / or a laptop 840 to receive information and notifications related to measurements made by the mat assembly 500.

[0092] Figure 13 depicts a sensing band 550 according to this disclosure. In one embodiment, a SEM sensor, such as sensor 90 or sensor 400 as described herein, is embedded in a band 554 that can be wrapped around a calf 60 as shown in Figure 13. In one embodiment, the band 554 comprises sensors configured to measure one or more of the tissue's oxygen supply, which may include measurements of oxyhemoglobin and deoxyhemoglobin, temperature, pulse rate, blood volume, and blood pressure at one or more points on the skin. In one embodiment, the combination of measurements made by the band 554 provides information about blood flow to the foot, where decreased blood flow is a possible indicator of susceptibility to DFU formation. In one embodiment, this information includes measurements of blood volume and replenishment time on a portion of the calf 60 adjacent to the band 554.

[0093] Figure 14A depicts an integrated sensor and stimulator assembly 201 suitable for the treatment of pressure ulcers according to the present disclosure. In one embodiment, the integrated sensor and stimulator assembly 201 is provided to a patient who needs it. 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 one embodiment, there are two electrodes 212A and 212B that are in conductive contact with the patient's (not shown in Figure 14A) skin when the assembly 201 is placed on the skin. These electrodes 212A, 212B are connected to an external controller (not shown in Figure 14A) configured to apply therapeutic electrical stimulation to the tissue between the electrodes 212A, 212B by stimulation applied for a period having a time interval between a certain duration and period. In one embodiment, low-level voltage and / or current may improve the healing of pressure ulcers. Each sensor 90 is individually connected to an external controller (not shown in Figure 14A) configured to measure the capacitance of each sensor 90. In one embodiment, the capacitance is measured at time intervals during the stimulation period. In one embodiment, the time interval can be in a typical range of several hours to several weeks. In one embodiment, the assembly 201 comprises an absorbent pad and a non-adhesive layer (not shown in Figure 14A) superimposed on the sensors 90 and electrodes 212A, 212B. In one embodiment, the assembly 201 comprises a layer of adhesive (not shown in Figure 14A) superimposed on a portion of the substrate 210 to allow the assembly 201 to be adhered to the patient's skin. In one embodiment, the substrate 201 may be permeable to gases but impermeable to liquids.

[0094] The combination of a standard bandage (absorbent pad, non-adhesive layer, and covering substrate) and therapeutic devices 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] Figure 14B depicts the sole of the foot 20 of a patient with a pressure ulcer 205.

[0096] Figure 14C depicts an assembly 201 adhered to the sole of a foot 20 across a pressure ulcer 205. In one embodiment, the assembly 201 is placed on the ulcer 205 and left in place for several days. In another embodiment, the assembly 201 includes a toroidal pad to relieve pressure on the pressure ulcer 205. External controllers for electrodes 212A and 212B are periodically attached to electrodes 212A and 212B to apply therapeutic stimulation. During the intervals between these stimulations, external controllers for sensors 90 are attached to one or more of the sensors 90 to produce SEM measurements.

[0097] In one embodiment, assembly 201 includes a battery and wireless communication capabilities that enable an external controller to apply stimulation through electrodes 212A, 212B without a wired connection to the assembly. Similarly, the assembly may be configured to enable the external controller to communicate with sensor 90 to produce and receive SEM measurements without a wired connection. In one embodiment, assembly 201 includes a microcontroller configured to apply therapeutic stimulation to produce 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 therapeutic devices and SEM sensors can be applied to other types of wounds and to other parts of the body other than the soles of the feet, such as the ankles or bony prominences.

[0099] Figure 14D depicts a bandage assembly 202, adapted to be placed over a pressure ulcer on the sacrum of a patient who requires it. The assembly 202 comprises a substrate 220 that is porous to gas but impermeable to liquid. The assembly 202 comprises a pad 222 (viewed from the outside in Figure 14D) that provides both protective padding and absorption. In this example, a single sensor 90 is positioned on the back surface of the pad 222 such that the sensor is just above the ulcer when the assembly is applied over an early-stage pressure ulcer containing undamaged skin. Electrodes 214A, 214B are placed adjacent to the sensor 90 and on the same back surface so as to be in contact with the patient's skin. In this configuration, the assembly 202 can be placed over an early-stage ulcer to protect and improve the healing process and monitor the progress of healing by removing the assembly 202 or interfering with the wound.

[0100] Although the present invention has been described in general terms, it will be more readily understood through reference to the following examples, which are provided graphically and are not intended to limit this disclosure unless otherwise noted. [Examples]

[0101] Example 1: Performing SEM measurements at multiple locations on the foot. To ensure complete electrode contact with the patient's skin, SEM measurements were performed on the foot using one of the following three methods.

[0102] Figure 15A illustrates a method used to perform SEM measurements beginning at the posterior heel using the apparatus according to this disclosure. First, the forefoot was dorsiflexed so that the toes pointed toward the shin. Second, the bioimpedance sensor 1520 was positioned at the base of the heel 1530. The electrode was adjusted to make full contact with the heel, and multiple SEM measurements were performed in a straight line toward the toes, including the balls of the toes of the foot 1540. The balls of the toes are one of the primary locations for diabetic foot ulcers.

[0103] Figure 15B illustrates a method used to perform SEM measurements starting at the lateral heel using the apparatus according to this disclosure. First, the foot was rotated inward toward the body, with the toes facing away from the body. Second, electrodes were positioned 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 performed in a straight line toward the sole of the foot. The ball of the toes of the foot 1540 is also shown in Figure 15B.

[0104] Figure 15C illustrates a method used to perform SEM measurements starting at the medial heel using the apparatus according to this disclosure. First, the foot was rotated outward toward the side of the body with the toes facing away from the body. Second, electrodes were placed on the medial surface 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 posterior part of the heel.

[0105] From the foregoing, it is understood 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 evaluating the susceptibility of tissue to the formation of diabetic foot ulcers, comprising: a plurality of electrodes embedded in a substrate, wherein a pair of electrodes can form a capacitance sensor, which is a capacitance sensor configured to measure a first capacitance of a first region of tissue adjacent to the capacitance sensor; a drive circuit electrically coupled to the electrodes; a processor electrically coupled to the drive circuit; and a non-temporary computer-readable medium electrically coupled to the processor and containing instructions stored in the non-temporary computer-readable medium, wherein when an instruction is executed on the processor, the device performs the steps of: receiving information about a measured first capacitance from the drive circuit; comparing the measured first capacitance with a first reference value; and providing a signal if the measured first capacitance differs from the first reference value by an amount exceeding a first predetermined threshold.

[0107] Embodiment 2. The apparatus according to Embodiment 1, wherein a first reference value is predetermined.

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

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

[0110] Embodiment 5. The apparatus according to Embodiment 1, wherein the first reference value is determined by measurements taken from symmetrical locations.

[0111] Embodiment 6. The apparatus according to Embodiment 1, wherein the first reference value is a measurement of the second capacitance of a second region of tissue that is separate from the first region of tissue.

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

[0113] Embodiment 8. The apparatus according to Embodiment 6, wherein the second capacitance is measured almost simultaneously with the first capacitance.

[0114] Embodiment 9. The apparatus according to Embodiment 1, further comprising one or more temperature sensors configured to measure the temperature of a first area of ​​tissue and coupled to a processor, wherein a command further includes the steps of receiving information about a measured temperature from one or more temperature sensors; comparing the measured temperature with a second reference value; and providing a signal if a measured first capacitance differs from the first reference value by an amount exceeding a predetermined first threshold, and the measured temperature differs from the second reference value by an amount exceeding a predetermined second threshold.

[0115] Embodiment 10. The apparatus according to Embodiment 1, further comprising one or more optical sensors configured to image the soles of the patient's feet while the patient is standing on a substrate.

[0116] Embodiment 11. A method for evaluating the susceptibility of tissue to the formation of diabetic foot ulcers, the method comprising: obtaining a first capacitance value at a first location on the 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 diabetic foot ulcers when the first capacitance value differs from a first reference value by an amount exceeding a first predetermined threshold, and the temperature measurement differs from a second reference value by an amount exceeding a second predetermined threshold.

[0117] Embodiment 12. The method according to Embodiment 11, wherein a first reference value is predetermined.

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

[0119] Embodiment 14. The method according to Embodiment 11, wherein the first reference value is determined from measurements of the 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 according to Embodiment 11, wherein the first reference value is a measurement of the second capacitance at a second location on the patient's skin, away from a first location on the patient's skin.

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

[0122] Embodiment 17. The method according to Embodiment 15, wherein the second capacitance is measured almost simultaneously with the first capacitance.

[0123] Embodiment 18. A method for evaluating the susceptibility of tissue to the formation of diabetic foot ulcers, the method comprising: obtaining a first subepidermal moisture (SEM) value at a first location on the 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 diabetic foot ulcers when the first SEM value differs from a first reference value by an amount exceeding a first predetermined threshold, and the temperature measurement differs from a second reference value by an amount exceeding a second predetermined threshold.

[0124] Embodiment 19. The method according to Embodiment 18, wherein a first reference value is predetermined.

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

[0126] Embodiment 21. The method according to Embodiment 18, wherein the first reference value is determined from first SEM value measurements 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 according to Embodiment 18, wherein the first reference value is a measurement of a second SEM value at a second location on the patient's skin, which is located away from a first location on the patient's skin.

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

[0129] Embodiment 24. The method according to Embodiment 22, wherein the second SEM value is measured almost simultaneously with the first SEM value.

[0130] Embodiment 25. An integrated device for treating diabetic foot ulcers in a patient in need thereof, comprising: a plurality of sensors disposed on a flexible substrate, each of which is configured to measure subepidermal moisture (SEM) values ​​at different locations on the patient's skin; two electrodes disposed 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 the SEM measurement period, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

[0131] Embodiment 26. The apparatus according to Embodiment 25, further comprising an absorbent pad.

[0132] Embodiment 27. The apparatus according to Embodiment 25, further comprising a layer of adhesive.

[0133] Embodiment 28. The apparatus according to Embodiment 25, wherein the flexible substrate is permeable to gas but impermeable to liquid.

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

[0135] Embodiment 30. The integrated apparatus according to Embodiment 29, wherein an external controller controls two electrodes to detect conductive contact with the patient's skin during the SEM measurement period, and the external controller controls two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

[0136] While the present invention has been described with reference to specific embodiments, those skilled in the art will understand that various modifications may be made, and elements may be replaced with equivalents, without departing from the scope of the invention. In addition, many modifications may be made to specific situations or materials for the teachings of the invention without departing from the scope of the invention. Accordingly, the present invention is not limited to the specific embodiments disclosed, but is intended to include all embodiments that fall within the scope of the appended claims and spirit.

Claims

1. An integrated device for treating diabetic foot ulcers in patients who require such treatment, wherein the integrated device is A sensor comprising a first electrode and a second electrode disposed on a molded substrate, wherein the sensor is configured to measure subepidermal moisture (SEM) values ​​at each location on the patient's skin during an SEM measurement period, the molded substrate is configured to fit snugly to a portion of the patient's foot, the measured SEM values ​​correspond to the extracellular fluid (ECF) levels at each location on the patient's skin during the SEM measurement period, and the sensor is 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 are disposed on the molded substrate, An external controller electrically connected to the third and fourth electrodes, wherein the external controller is configured to control the third and fourth electrodes to detect conductive contact with the patient's skin during the SEM measurement period, and the external controller is configured to control the third and fourth electrodes to apply therapeutic stimulation to the patient during the treatment phase, wherein the therapeutic stimulation is applied over a plurality of periods, the plurality of periods having a duration and a time interval between the plurality of periods, and the therapeutic stimulation is a low-level voltage or low-level current that improves the healing of the diabetic foot ulcer. An integrated device equipped with the following features.

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

3. The integrating apparatus according to claim 1 or 2, wherein the molded substrate is integrated into the lining of a garment.

4. The integrating apparatus according to claim 1 or 2, wherein the molded substrate is integrated into the sole of a shoe.

5. The integrating apparatus according to claim 1 or 2, wherein the molded substrate is integrated into a sensing band.

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

7. The integrated device according to any one of claims 1 to 6, further comprising the ability to wirelessly communicate with a Wi-Fi access point.

8. The integrated apparatus according to any one of claims 1 to 7, further configured to communicate with one or more SEM applications running on one or more digital devices such as a server, computer, laptop computer, or smartphone.

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

10. The integrated apparatus according to claim 8 or the integrated system according to claim 9, wherein the one or more digital devices are selected from a group consisting of servers, computers, laptop computers, and smartphones.

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

12. The integrated apparatus according to claim 1, further comprising an absorbent pad.

13. The integrating apparatus according to claim 1 or 12, further comprising a layer of adhesive.

14. The integrating apparatus according to claim 1, 12, or 13, wherein the molded substrate is permeable to gas but impermeable to liquid.

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