Measurement of susceptibility to diabetic foot ulcers

Abstract

To provide an apparatus and a method for measuring capacitance as an indicator of susceptibility to the formation of diabetic foot ulcers.SOLUTION: An integrated apparatus for performing treatment of a diabetic foot ulcer in a patient in need thereof, the integrated device comprising a plurality of sensors disposed on a flexible substrate, the plurality of sensors configured to measure sub-epidermal water (SEM) values at respective locations of the patient's skin during a SEM measurement period, a first electrode and a second electrode disposed on the flexible substrate, and an external controller electrically connected to the first electrode and the second electrode, wherein the external controller is configured to control the first electrode and the second electrode to detect contact with the patient's skin by determining a capacitance during the SEM measurement period, and wherein the external controller is configured to control the first electrode and the second electrode to apply therapeutic electrical stimulation to the patient during a treatment phase.SELECTED DRAWING: Figure 1A

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 Feb. 3, 2017, and U.S. Provisional Application No. 62 / 521,917, filed on Jun. 19, 2017, each of which is hereby incorporated by reference in its entirety.

[0002] The present disclosure provides an apparatus and a method for evaluating a foot of a patient at risk of developing a diabetic foot ulcer.

Background Art

[0003] Diabetic foot ulcers are the cause of more hospitalizations than any other complication of diabetes. Non - enzymatic glycosylation induced by elevated blood glucose 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 a loss of protective sensation and a loss of the coordination of muscle groups in the foot and leg. 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 sense pain usually 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 for preventing diabetic foot ulcers are patient education, foot and toenail care, appropriate footwear selection, and prophylactic surgical measures. Detection means for pre-ulcer states may enable implementation of preventive techniques such as load relief and improved hygiene. SUMMARY OF THE INVENTION

[0006] In one aspect, the present disclosure provides and includes an apparatus for assessing tissue sensitivity to the formation of diabetic foot ulcers, the apparatus comprising a plurality of electrodes embedded in a substrate, a pair of the electrodes being a capacitance sensor configured to measure a first capacitance of a first region of tissue proximate the capacitance sensor, the plurality of electrodes capable of forming 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 including instructions stored thereon, the instructions including receiving, from the circuit, information regarding the first capacitance measured by the capacitance sensor when executed on the processor, comparing the measured first capacitance with a first reference value, and providing a signal when the measured first capacitance differs from the first reference value by an amount exceeding a first predetermined threshold.

[0007] In one aspect, the present disclosure provides and includes a method for assessing tissue sensitivity to the formation of diabetic foot ulcers, 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 sensitive 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 value differs from a second reference value by an amount exceeding a second predetermined threshold.

[0008] In one aspect, the present disclosure provides, and includes, a method for evaluating tissue susceptibility to the formation of diabetic foot ulcers, the method comprising obtaining a first sub-epidermal moisture (SEM) 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 diabetic foot ulcers when the first SEM 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.

[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 being configured to measure sub-epidermal 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 a therapeutic stimulus to the patient during a treatment stage.

[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 two electrodes disposed on a flexible substrate such that a current passing between the electrodes will pass through tissue proximate to a location on the patient's skin, a sensor, and an external controller electrically connected to the two electrodes. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Aspects of the present disclosure are described herein by way of example only with reference to the accompanying drawings. Specific reference will now be made in detail to the drawings, it being emphasized that the items shown are examples and are for the purpose of illustration of aspects of the present disclosure. In this regard, the description and the drawings, alone or in combination, will make it apparent to those skilled in the art how aspects of the present disclosure may be implemented.

[0012]

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DETAILED DESCRIPTION OF THE INVENTION

[0013] The present disclosure describes the measurement of various electrical characteristics and the derivation of SEM values indicative of an increase in the amount of ECF, as well as the application of this information to the evaluation of the sensitivity to the treatment of diabetic foot ulcers and ulcers.

[0014] Diabetic foot ulcers are known to occur in areas exposed to repetitive moderate loads, particularly in bony parts of the foot where adjacent tissues are subjected to weight transfer while standing. Since the damage may initially occur in the tissues under the skin, it cannot be detected by visual inspection. The initial damage will release fluid into the extracellular space and can be detected through the measurement of the electrical properties of the subepidermal tissue, such as the capacitance of the tissue. Monitoring of ECF in potentially dangerous areas will detect tissue deterioration that, if left undetected, will progress to open ulcers.

[0015] This description is not intended to be an exhaustive 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. Further, numerous modifications and additions to the various embodiments proposed herein will be apparent to those skilled in the art in light of the present disclosure, and these do not depart from the present disclosure. In other instances, well-known structures, interfaces, and processes are not shown in detail so as not to unnecessarily obscure the present invention. No part of this specification is intended to be construed as denying any part of the full scope of the present invention. Accordingly, the following description is intended to illustrate some particular embodiments of the present disclosure and is not intended to specifically identify all substitutions, combinations, and modifications 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 the description of the disclosure herein is for the purpose of describing particular aspects or embodiments only and is not intended to limit the disclosure.

[0017] All publications, patent applications, patents, and other references cited herein are hereby incorporated by reference in their entirety for the teachings relevant to the passages and / or paragraphs in which the references are presented. References to techniques used herein are intended to refer to techniques as commonly understood in the art, including variations or equivalent techniques substitutions for these techniques, which would be apparent to those skilled in the art.

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

[0019] U.S. Patent Application No. 15 / 134,110 discloses an apparatus for measuring subcutaneous moisture (SEM) similar to the device shown in FIG. 3C, where 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 to an SEM value.

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

[0021] It is clearly intended that, unless otherwise indicated, 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 can be excluded or omitted.

[0022] The methods disclosed herein include and comprise one or more steps or acts for achieving the described methods. The steps and / or acts of the methods are interchangeable with each other without departing from the scope of the invention. In other words, the order and / or use of specific steps and / or acts can be modified without departing from the scope of the invention, unless a specific order of steps or acts is required for the correct operation of the embodiment.

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

[0024] As used herein, "and / or" refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the absence of combinations when interpreted in another way ("or").

[0025] As used herein, terms such as "about" and "approximately" when referring to measurable values such as length, frequency, or SEM values are meant to encompass 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 between X and Y" should be interpreted to include X and Y. As used herein, phrases such as "about between X and Y" mean "between about X and about Y", and phrases such as "about X - Y" mean "about X - about Y".

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

[0028] As used herein, a "system" can be an assembly of devices that communicate with each other, either wired or wirelessly.

[0029] As used herein, "examining" refers to the use of radiofrequency energy that penetrates a patient's skin.

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

[0031] As used herein, "being healthy" can describe tissue that does not exhibit symptoms of damage to cell walls or blood vessels, where the presence of an increased amount of ECF is an indicator of such damage.

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

[0033] As used herein, "sensitive to the formation of diabetic foot ulcers" may describe a tissue that exhibits symptoms of damage to cell walls or blood vessels, such as edema or increased amounts of ECF, but does not have an open ulcer.

[0034] As used herein, "time point_0" refers to an initial time point, for example, when an open ulcer is first detected.

[0035] As used herein, "time point_1" refers to a time point that is later than time point_0.

[0036] As used herein, "time point_2" refers to a time point that is later than time point_1.

[0037] Figure 1A is a side 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 under the calcaneus 21 and the ball of the foot located under the midfoot bone 22.

[0038] Figure 1B is an enlarged view of area "A" of Figure 1A. The ends of the midfoot bone 22 and the adjacent phalanx 23 are shown close to the skin 24 on the back of the foot 20. A portion of the patient's body weight creates a compressive force 30 applied by the midfoot bone 22 to the tissue within region 40. The force 30 is counteracted by a resistance force 36 applied by the floor to the skin 24 under region 40 to support the patient. Muscle activity by a patient who is walking on their foot while standing or simply maintaining balance creates a shear force 32 between the midfoot bone 22 and the tissue 40, as well as a resistive shear force 38 between the floor and the skin 24. Thus, the tissue within region 40 is simultaneously exposed to both compressive and shear forces.

[0039] Healthy patients are observed to shift their weight from foot to foot and shift the center of their mass with respect to their feet while standing still. 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 and thus reduces the unconscious shifting of the patient's weight, and patients suffering from peripheral neuropathy are observed to lack normal movement while standing. This results in a prolonged duration of the continuous compressive force applied to local areas of tissue such as area 40. Being exposed to a moderate level of force for a long period of time is thought to cause 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 initial open ulcer 50A at time point _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 shoe the patient is wearing is applied locally as a uniform pressure 56 to the skin 24 of the foot 20. The applied pressure 56 is counteracted internally by the force 53. When the tissue has peeled away, pressure cannot be applied onto the ulcer 50. Thus, the internal force in the toroidal region 52A increases to a peak 54 and obtains 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. When the body tries to protect itself from the increased pressure, subperiosteum will generally form across the area 52A. However, the tissue under the subperiosteum is still damaged and will show an increase in ECF.

[0042] Figure 2C depicts the same region of the tissue at time point _1 following time point _0. The increase in the pressure level in region 52A results in tissue death in region 52A, and the tissue in region 52 peels off, so that ulcer 50B becomes larger than the previous ulcer 50A. The applied pressure 56 has not changed, but for this reason, the tissue in region 52B around the larger ulcer 50B needs to obtain a greater force. As a result, the tissue in region 52B dies more rapidly under a greater applied load, accelerating the expansion of ulcer 50.

[0043] Figure 2D depicts the same region of the tissue as in Figures 2A and 2C at time point _2 following time point _1. Ulcer 50 has increased to size 50C of increased pressure and region 52C, which is larger than the previous regions 52A, 52B.

[0044] In the situation shown in Figure 2A where an ulcer has formed, therapeutic measures will be introduced to prevent the enlargement of ulcer 50 and enable the body to heal the open ulcer 50. The treatment may involve placing a pressure relief pad around the ulcer to spread the pressure 56 over a larger area of healthy tissue and eliminate the peak 54 that causes further damage. However, the determination of whether the treatment is functioning can only be made by observing over time that the ulcer is not progressing.

[0045] Figure 3A discloses a toroidal bioimpedance sensor 90. In this exemplary configuration, the central electrode 110 is surrounded by the 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 under the sensor 90. In one aspect, the ground plane (not visible in Figure 3A) is parallel to and spaced from the electrode surface, and in one aspect, it extends beyond the outer diameter of the ring electrode 120. Without being limited to a particular theory, the ground plane may limit the electric field between the electrodes 110 and 120 to a single side of the surfaces of the electrodes 110 and 120 opposite to the side of the ground plane.

[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 outwardly from the surfaces of electrodes 110 and 120 to the depth of electric field 150. The diameter of central electrode 110, the inner and outer diameters of toroidal electrode 120, and the gap between electrodes 110 and 120 can be varied to change the characteristics of electric field 140, such as the depth of electric field 150.

[0047] In use, the drive circuit can measure an electrical property or parameter that includes one or more electrical characteristics selected from the group consisting of resistance, capacitance, inductance, impedance, magnetoresistance, and other electrical characteristics as sensed by electric field 140. Depending on the type of drive circuit used in the device, the sensor of the device can be a bipolar radio frequency sensor, a bioimpedance sensor, a capacitance sensor, or a SEM sensor. In one aspect, the measured electrical parameter is related 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 electric field 140, and other operating characteristics of the drive circuit of the device. In one aspect, the measured moisture content is equivalent to a SEM content having a value on a given scale. In one aspect, the given scale can be in the range of 0 - 20, such as 0 - 1, 0 - 2, 0 - 3, 0 - 4, 0 - 5, 0 - 6, 0 - 7, 0 - 8, 0 - 9, 0 - 10, 0 - 11, 0 - 12, 0 - 13, 0 - 14, 0 - 15, 0 - 16, 0 - 17, 0 - 18, 0 - 19. In one aspect, the given scale can be determined by one or more factors based on the values provided herein. In one aspect, multiple measurements are taken while varying one or more of these operating characteristics during the reading, thereby providing information related to the moisture content at various depths of the skin.

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

[0049] In certain embodiments, the region is defined by a surface area. In certain embodiments, the region is, for example, 5 - 200 cm 2 , 5 - 100 cm 2 , 5 - 50 cm 2 , or 10 - 50 cm 2 , 10 - 25 cm 2 , or 5 - 25 cm 2 and may be.

[0050] In certain embodiments, the measurements may be made in a specific pattern or a portion thereof. In certain embodiments, the pattern of readings is made in a pattern that includes a central target area of interest. In certain embodiments, the 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 certain embodiments, the pattern may be placed on the body by defining a first measurement location of a pattern regarding an anatomical feature that includes the remaining measurement locations of the pattern defined as an offset from the first measurement value location.

[0051] In certain embodiments, a plurality of measurements are taken across a tissue or region, and the difference between the lowest and highest measurement values of the plurality of measurements is recorded as the delta value of the plurality of measurements. In certain embodiments, 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 value can 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 values can be established for at least one region. In some embodiments, a delta value is specified as being significant when the delta values of multiple measurements within a region meet or exceed a 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 can have a common threshold value.

[0053] In some embodiments, the threshold value has both a delta value component and a component over time, where the delta value is specified as being significant when the delta value exceeds a predetermined numerical value for a predetermined portion of the time interval. In some embodiments, the predetermined portion of the time interval is defined as the minimum value of X days in which multiple measurements taken on that day produce delta values that are greater than or equal to a predetermined numerical value 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 in which multiple measurements taken on that day produce delta values that are greater than or equal to a predetermined numerical value. In some embodiments, the predetermined portion of the time interval can be defined as a portion of a different specific period (week, month, hour, etc.).

[0054] In some embodiments, the threshold value has a trend aspect in which the changes in the delta values of multiple consecutive measurements are compared to each other. In some embodiments, the trend threshold value is defined as a predetermined change in the delta value that exceeds a predetermined length of time, where the determination of whether the threshold value is met or exceeded is significant. In some embodiments, a warning will be issued based on the determination of significance. In some embodiments, a trend line can be calculated from a portion of the individual measurement values of multiple consecutive measurements. In some embodiments, a trend line can be calculated from a portion of the delta values of multiple consecutive measurements.

[0055] In some embodiments, the number of measurements taken within a single region may be less than the number of measurement locations defined as a pattern. In some embodiments, the 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 in a region 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 region may be greater than the number of measurement locations defined by a pattern. In some embodiments, the delta value will be calculated after each additional reading.

[0057] In some embodiments, quality measurement criteria may be generated for each of the plurality of measurements. In some embodiments, this quality measurement criteria is selected to evaluate the repeatability of the measurements. In some embodiments, this quality measurement criteria is selected to evaluate the skill of the clinician who performed the measurements. In some embodiments, the quality measurement criteria may include one or more statistical parameters, such as an average, mean value, or standard deviation. In some embodiments, the quality measurement criteria may include one or more comparisons of individual measurement values to a predefined range. In some embodiments, the quality measurement criteria may include a comparison of individual measurement values to a pattern of values, such as a comparison of a measurement value at a predefined location to a range associated with each predefined location. In some embodiments, the quality measurement criteria may include a determination of which measurement values were made across healthy tissue and one or more evaluations of the consistency within this subset of "healthy" measurement values, such as a range, standard deviation, or other parameter.

[0058] In one embodiment, the measurement value, e.g., the threshold value, is determined by an SEM scanner model 200 (Bruin Biometrics, LLC, Los Angeles, CA). In another embodiment, the measurement value is determined by another SEM scanner.

[0059] In some embodiments, the measured value is based on a capacitance measurement value by referring to a reference device. In some embodiments, the capacitance measurement value may depend on the location of any electrode of the device and other embodiments. Such variations can be compared with a reference SEM device such as an SEM scanner model 200 (Bruin Biometrics, LLC, Los Angeles, CA). Those skilled in the art understand that the measured values described herein can be adjusted to match the differential capacitance range by referring to a reference device.

[0060] FIG. 3C provides a top view and a bottom view of an SEM scanner 170 including an electronic device that drives a sensor 174 similar to the sensor 90 of FIG. 3A and measures 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 WO2016 / 172263, to which U.S. Patent Application No. 15 / 134,110 was filed as a national stage entry, and all of them are hereby incorporated by reference in their entirety.

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

[0063] Regardless of whether any pair of electrodes is composed of a single electrode or a set of electrodes coupled together to form a virtual electrode, an electronic device (not shown in FIG. 4) configured to measure electrical properties or parameters including resistance, capacitance, inductance, impedance, magnetoresistance, or one or more of sensors 90, 174, 290, 430, 440, or one or more of other electrical characteristics including other two - electrode sensors is coupled thereto. The electronic device of the present disclosure may be further configured to compare a measured first capacitance to a reference value and provide a signal if the measured capacitance differs from the reference value by an amount that exceeds a threshold value. In one aspect, 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 substantially hexagonal and is separated from each of the surrounding electrodes 410 by a gap 420. In one aspect, the electrodes 410 are one of circular, square, pentagonal, or other regular or irregular shapes. In certain aspects, the gaps 420 are uniform among all the electrodes 410. In one aspect, the gaps 420 vary among the different electrodes. In one aspect, the gap 420 has a width that is narrower than the cross-section of each of the electrodes 410. The electrodes 410 can be interconnected to form virtual sensors 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 a center electrode, and the ring of electrodes 410 marked with "2" are interconnected to form a ring electrode. In certain aspects, the electrodes 410 between the center electrode and the ring electrode are electrically "floating." In one aspect, the electrodes 410 between the center electrode and the ring electrode are grounded or connected to a floating ground. In certain aspects, the electrodes 410 outside the ring electrode are electrically "floating." In one aspect, the electrodes 410 outside the virtual ring electrode are grounded or connected to a floating ground.

[0066] FIG. 6B depicts an alternative aspect in which an array 400 of electrodes 410 is configured to form a virtual sensor 440 according to the present disclosure. In certain aspects, a plurality of electrodes 410 indicated by "1" are interconnected to form a center electrode, and the ring of electrodes of twice the width indicated by "2" are interconnected to form a ring electrode. In one aspect, various numbers and positions of electrodes 410 are interconnected to form virtual electrodes of various sizes and shapes.

[0067] Figures 6A and 6B depict an exemplary configuration of an electrode array 400 that can form sensors 430 at multiple overlapping locations according to the present disclosure. In Figure 6A, a virtual sensor 430A is formed by a central electrode 432 formed by a single electrode 410 indicated by "1" and a ring electrode 434 formed by a plurality of electrodes 410 indicated by "2". The same array 400 is shown in Figure 6B, where a new virtual sensor 430B is formed by a central electrode 436 indicated by "3" and a ring electrode 438 indicated by "4". The position of the virtual sensor 430A is indicated by a black contour. It can be seen that the virtual sensor 430B overlaps the position of the virtual sensor 430A, which enables measurements to be made with a resolution finer than the diameter of the sensor 430.

[0068] Figure 6E shows a method by which a sensor 430 can be formed from an array of electrodes 400 that is larger than a portion of a patient's skin positioned relative to the array. In this example, the outline of a contact area 450 of the back 22R of the patient's right foot as seen from directly below 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. At such a position, the capacitance or other electrical parameter measured by the sensor 430C is lower than the capacitance measured by a sensor 430D that is fully positioned within the contact area 450. It can be seen that the sensor 430 can be formed at any point within the array 400 and can 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 aspect, the two sensors can 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 aspect, the two sensors can 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 aspect, the two sensors can 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 can further include a plurality of contact sensors (not shown in FIG. 6E) on and surrounding each of the electrodes on the same flat surface as the electrodes to ensure complete contact of one or more virtual sensors with the skin surface. The plurality of contact sensors can be a plurality of pressure sensors, a plurality of optical 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 stimulation device sensors, or a plurality of combinations of these sensors. In some embodiments, the plurality of contact sensors can include 4, 5, 6, 7, 8, 9, or 10 or more contact sensors surrounding each electrode.

[0071] Figures 6F and 6G depict an example of a method according to the present disclosure in which a comparison of SEM values associated with sensors at known associated locations can identify bilaterally symmetric locations. In this example, sensors 430 are formed in non-overlapping locations and are marked with letters "A" through "H" in Figure 6F across the contact area 450R of the right foot 20R. The SEM values measured at each location are plotted on 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 that include the 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 the contact area 450 at these positions. 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 fully within the contact area 450 at these locations. In one aspect, an SEM measurement device, such as device 180, can determine that certain locations, for example, locations "C" and "F", are bilaterally symmetric with respect to the centerline 452R of the right foot 20R. In one aspect, where a similar set of measurements is made at locations A'-H' on the left foot 20L, the locations on each foot 20L and 20R, for example, locations E and E', can be determined to be approximately bilaterally symmetric.

[0072] FIG. 7A depicts an exemplary mat assembly 500 incorporating a plurality of bio-impedance sensors 520 according to the present disclosure. The sensors 520 are shown as toroidal sensors similar to the sensor 90 depicted in FIG. 3A, but the sensors 520 can be any configuration of electrical measurement sensors including the configurations shown in FIGS. 4, 5, and 6A-6B. The sensors 520 are distributed across the substrate 510. In some embodiments, a portion of the substrate 510 is flexible. In one embodiment, a portion of the substrate 510 is rigid. In some embodiments, the electrodes of the sensors 520 are electrically bare, thereby enabling conductive electrical contact with the patient's feet when the patient stands 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 enabling only capacitive electrical contact with the patient's feet when the patient stands 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 installed together with the SEM sensors 520 to provide the temperature and SEM measurements at a common location.

[0074] In one aspect of the mat assembly 500, a signal is provided when the measured capacitance differs from the reference capacitance value by an amount that exceeds a first threshold and the measured temperature differs from the temperature reference value by an amount that exceeds a second threshold. In some aspects, one or both of the thresholds are predetermined. In one aspect, the first threshold is set to 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 reference capacitance value. In one aspect, the second threshold is set to 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 reference temperature value. In one aspect, one or both of the capacitance and temperature reference values are determined from the rolling average of the last five sequential measurements, for example, the average of a plurality of measurements made during a previous period, such as a month earlier, where the previous measurements are used.

[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, when a clinician examines a tissue and determines that the tissue is healthy, i.e., not susceptible to the formation of diabetic foot ulcers, such as while in a physician's examination room.

[0076] FIG. 7B depicts another exemplary mat assembly 502 comprising arrays 530L and 530R of electrical sensors 520, where arrays 530L and 530R are disposed such that while standing on mat assembly 502, they are respectively under a patient's left and right feet. In one aspect, left and right foot contours 540L and 540R are depicted across arrays 530L and 530R to guide a patient standing in the correct location.

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

[0078] In one aspect, substrate 510 is partially transparent and mat 504 comprises a second substrate 512 to which one or more optical sensors 550 are attached. In one aspect, optical sensor 550 is a camera capable of imaging the underside of a patient's foot while standing on mat 504. In one aspect, optical sensor 550 is sensitive to visible light. In one aspect, optical sensor 550 is sensitive to infrared light.

[0079] Regular use of mat assemblies 500, 502, 504, etc. by a patient can serve to detect changes in the patient's foot health. For example, at the time of examination by a clinician 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. Next, the patient places 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 foot by sensor 520. When the patient stands in the same location, for example, as guided by contours 540L and 540R, each sensor 520 and 550 measures the same location for each repeated measurement. In one aspect, 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 aspect, an image is captured in mat assembly 504 by light sensor 550. This information is stored in local memory or transmitted to a remote storage location such as a physician's examination room. Each daily measurement is compared to a reference value derived from an average of previous measurements, for example, measurements made in a clinician's examination room or measurements from the previous week. If the latest measurement deviates from the reference value, the patient is reported of that deviation. The patient can then seek advice from the clinician regarding further evaluation and possible measures. In one aspect, a change in the measured SEM value greater than a threshold triggers a notification. In one aspect, both a change in the measured SEM value greater than a first threshold and a change in the measured temperature greater than a second threshold trigger a notification. In one aspect, 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 aspect, the first threshold is set to 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 reference SEM value. In one aspect, the second threshold is set to 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 reference temperature value. In some aspects, information such as an image of the back of the patient's foot is always sent to the clinician for review.

[0080] In some aspects, the measurements of the left and right feet are compared to each other. For example, referring to FIGS. 6F and 6G, locations E and E' are compared to each other. In one aspect, the difference between the left and right measurements is compared to a reference value, and if the difference exceeds a threshold, the patient is notified.

[0081] FIG. 8A discloses a foot cover 600 incorporating a bio - impedance sensor 520 as shown in the cross - sectional view of FIG. 8B. In one aspect, the foot cover 600 comprises a sock or other flexible form - fitting garment 610 into which a foot can be inserted. In one aspect, 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 aspect, the flexible form - fitting garment 610 may be a conventional shoe, such as a leather shoe or a sneaker. The sensor 520 is placed at one or more locations corresponding to areas of interest for ulcer development. In one aspect, the sensor 520 is placed under or around the heel of the flexible form - fitting garment 610. In one aspect, the sensor 520 is placed on the back of the flexible form - fitting garment 610. In one aspect, the sensor 520 is placed in the area around the toes (not visible in FIG. 8B) of the flexible form - fitting garment 610.

[0082] FIG. 9 discloses a sandal 650 incorporating a bio - impedance sensor 520 according to the present disclosure. One or more sensors 520 are disposed on the sandal at locations corresponding to areas of potential ulcer development.

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

[0084] FIG. 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 a plurality of electrodes 710 are connected to form a ring electrode 732 having a gap 742 that is larger in diameter than the ring electrode 730 and 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] FIG. 10C depicts a third exemplary configuration 704 of the same array of sensors 710 where one electrode is connected to form the central electrode 724 and a plurality of electrodes 710 are connected to form a ring electrode 734 having a diameter larger than that of the ring electrodes 730 and 732 and a gap 744 larger than the gaps 740 and 742. The sensor configuration 704 will have a third electric field depth 150 that is larger than either of the sensor configurations 700 or 702.

[0086] In one aspect, the mat assembly 500 comprises an array of electrodes 710 distributed across a portion of the 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 form the sensor configuration 700, make a first measurement, and then reconfigure the electrodes 710 to form the sensor configuration 702 and make a second measurement. The first and second measurements provide information about the difference in ECF at different depths under the skin of the foot, thereby providing improved knowledge of the tissue state within the foot. In one aspect, the mat assembly 500 is then configured to form the sensor configuration 704 and make a third measurement. Comparison of the three measurements provides even greater resolution of the internal tissue state.

[0087] Figures 11A and 11B depict exemplary aspects of a sensor assembly 500 configured to be disposed at a known location on a patient's skin. In this example, the sensor assembly 500 has a molded substrate 510 configured to fit snugly against the rear and bottom surfaces of the heel of the foot 20. In one aspect, the molded 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 inner surface of the molded substrate 510. In this example, the sensor 520 is configured as a toroidal sensor as shown in FIG. 1A. In one aspect, the inner surface of the molded substrate 510 is aligned with an array 400 of electrodes 410 such that virtual sensors can be formed anywhere, as shown in reference to FIG. 5. In one aspect, sensors of other shapes and configurations are provided on the inner surface of the molded substrate 510. In one aspect, the molded substrate 510 is a flexible panel (not shown in FIG. 11A) that can fit snugly against the patient's skin and can be wrapped around, for example, the back of the ankle. In one aspect, 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 characteristics, a processor, a communication subsystem, or other types of electronic assemblies (not shown in FIG. 11A).

[0088] FIG. 11B depicts an exemplary configuration of a sensor assembly 500 in which a plurality of sensors 520 are disposed on a shaped substrate 510, such as when the sensor assembly 500 is disposed against the skin of a patient around the rear, side, and bottom of the center of the right heel. This enables multiple SEM measurements to be taken at repeatable locations on the heel having the sensor assembly 500 at a single location. In one aspect (not shown in FIGS. 11A and 11B), the sensor assembly 500 is configured to be disposed on a portion of the rear of the patient, thus providing the ability to make measurements at symmetric locations on the rear. In certain aspects, the shaped substrate 510 is configured to conform to the anatomical features of the target area of the patient. In one aspect, the shaped substrate 510 includes a mark or other indicator that may conform to the characteristics of the patient's body so as to enable measurements to be taken at the same location at time intervals within a general range of hours to weeks. In one aspect, the sensor assembly 500 is integrated into clothing or footwear or other clothing linings. In certain aspects, the sensor assembly 500 is integrated into sheets, blankets, liners, or other types of bedding. In one aspect, the sensor assembly 500 includes wireless communication capabilities, such as passive radio frequency identification (RFID) or inductive coupling, to enable operation of the sensors 520 without a physical connection to the sensor assembly 500.

[0089] In certain aspects, the sensors 520 are coupled to an electronic device (not shown in FIG. 11B) configured to compare a current set of measurements with each other and with past measurements made at the same location. In certain aspects, the electronic devices of the present disclosure may provide a signal when one or more of a certain set of 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 a previous time point, 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 the measurement, evaluation, storage, and transmission of SEM values according to the present disclosure. In this example, system 800 includes an SEM measurement device 810, such as an SEM scanner 170, that has the ability to communicate wirelessly 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 some embodiments, laptop computer 840 and smartphone 830 are carried by a user of device 810, such as a nurse, and the application provides feedback and information to the user. In some embodiments, information about a patient received from device 180 is stored within database 850. In one embodiment, information about a patient received from device 810 is stored within database 860. In some embodiments, information received from device 810 is transferred via network 855 to another server 880 that stores a portion of the information within an electronic medical record (EMR) 870 of the patient. 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, such as the computer in a physician's examination room treating the patient.

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

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

[0093] Figure 14A depicts an integrated sensor and stimulation device assembly 201 suitable for the treatment of pressure ulcers according to the present disclosure. In one aspect, the integrated sensor and stimulation device 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 sub-epidermal moisture (SEM) as an indicator of tissue health at the location of each sensor 90. In one aspect, there are two electrodes 212A and 212B that are in conductive contact with the skin of a patient (not shown in Figure 14A) 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 a stimulation applied for a duration and at intervals having a period. In one aspect, low-level voltage and / or current may improve the healing of pressure ulcers. The sensors 90 are individually connected to an external controller (not shown in Figure 14A) configured to measure the capacitance of each sensor 90. In one aspect, the capacitance is measured at intervals during the stimulation period. In one aspect, the time interval can be in the general range of several hours to several weeks. In one aspect, the assembly 201 includes an absorbent pad and a non-adhesive layer (not shown in Figure 14A) superimposed on the sensors 90 and the electrodes 212A, 212B. In one aspect, the assembly 201 includes a layer of adhesive (not shown in Figure 14A) superimposed on a portion of the substrate 210 to enable the assembly 201 to be adhesively attached to the patient's skin. In one aspect, the substrate 201 may be permeable to gas but impermeable to liquid.

[0094] A combination with a therapeutic device such as a standard dressing (absorbent pad, non-adhesive layer, and coated substrate) and an external controller associated with the electrodes 212A, 212B and 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 underside of the foot 20 of a patient having a pressure ulcer 205.

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

[0097] In one aspect, 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 can be configured such that an external controller can communicate with sensor 90 to generate and receive SEM measurements without a wired connection. In one aspect, assembly 201 comprises a microcontroller configured to apply therapeutic stimulation, generate 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 underside of the foot, such as the ankle or a bony prominence.

[0099] FIG. 14D depicts a bandage assembly 202 adapted to be placed across a pressure ulcer on the sacrum of a patient in need thereof. The assembly 202 includes a substrate 220 that is porous to gas but impermeable to liquid. The 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 back surface of the pad 222 such that when the assembly is applied over an incipient stage pressure ulcer including intact skin, the sensor is directly over the pressure ulcer. Electrodes 214A, 214B are placed on the same back surface adjacent to the sensor 90 so as to contact the patient's skin. In this configuration, the assembly 202 can be placed over an incipient stage ulcer, protect and improve the healing process, and monitor the progress of healing by removal of the assembly 202 or interference with the wound.

[0100] While the invention has been generally described, 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 present 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 a human patient, SEM measurements were performed on the foot using one of the following three methods.

[0102] FIG. 15A illustrates a method used to perform SEM measurements starting at the posterior heel using the apparatus according to the present disclosure. First, the forefoot was dorsiflexed such that the toes pointed towards the tibia. Second, the bioimpedance sensor 1520 was positioned at the base of the heel 1530. The electrodes were adjusted to make complete contact with the heel, and a plurality of SEM measurements were taken in a straight line towards the toes, including the metatarsal heads of the foot 1540. The metatarsal heads of the foot are one of the major locations of diabetic foot ulcers.

[0103] Figure 15B illustrates a method used to perform SEM measurements starting from the lateral heel using the device according to the present disclosure. First, the toes were directed away from the body and rotated inwardly toward the inside of the body. Second, an electrode was placed on the lateral side of the heel 1550. The bio-impedance sensor 1520 was adjusted to be in complete contact with the heel, and a plurality of 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] Figure 15C illustrates a method used to perform SEM measurements starting from the medial heel using the device according to the present disclosure. First, the toes were directed away from the body and rotated outwardly toward the lateral side of the body. Second, an electrode was placed on the inside of the heel 1560. The bio-impedance sensor 1520 was adjusted to be in complete contact with the heel, and a plurality of measurements were taken in a curve around the rear portion of the heel.

[0105] From the foregoing, it is understood that the present invention can be embodied in various ways, and these ways include, but are not limited to, the following.

[0106] Embodiment 1. An apparatus for evaluating tissue sensitivity to the formation of diabetic foot ulcers, the apparatus comprising: a plurality of electrodes embedded in a substrate, a pair of which form a capacitance sensor configured to measure a first capacitance of a first region of 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 storing instructions including: receiving, from the drive circuit, information regarding the measured first capacitance; 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.

[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 measured value of a first capacitance when a first region of the tissue is healthy.

[0109] Embodiment 4. The apparatus according to Embodiment 1, wherein the first reference value is determined from measured values of the first capacitance in the first region of the tissue at one or more time points before the latest measurement of the first capacitance.

[0110] Embodiment 5. The apparatus according to Embodiment 1, wherein the first reference value is determined by measured values from symmetric locations.

[0111] Embodiment 6. The apparatus according to Embodiment 1, wherein the first reference value is a measured value of a second capacitance of a second region of the tissue that is distant from the first region of the 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 substantially 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 the first region of the tissue and coupled to the processor, the instructions further including receiving information regarding the measured temperature from the one or more temperature sensors, comparing the measured temperature with a second reference value, and providing a signal when the 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 device according to Embodiment 1, further comprising one or more optical sensors configured to image the back surface of the patient's foot while the patient is standing on the substrate.

[0116] Embodiment 11. A method for evaluating the sensitivity 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 value at the first location on the patient's skin, and determining that the first location on the patient's skin is sensitive 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 value differs from a second reference value by an amount exceeding a second predetermined threshold.

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

[0118] Embodiment 13. The method according to Embodiment 11, wherein the first reference value is determined by a measurement value of the 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 measurement values of the first capacitance at the first location on the patient's skin at one or more time points before 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 value of the second capacitance at a second location on the patient's skin that is remote from the first location on the patient's skin.

[0121] Embodiment 16. The method according to Embodiment 15, wherein it is known that the second region of the patient's skin is healthy.

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

[0123] Embodiment 18. A method for evaluating the sensitivity of tissue to the formation of diabetic foot ulcers, the method comprising obtaining a first sub-epidermal moisture (SEM) 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 sensitive 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 value differs from a second reference value by an amount exceeding a second predetermined threshold.

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

[0125] Embodiment 20. The method according to Embodiment 18, wherein the first reference value is determined by a measured value of the first SEM value 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 measured values of the first SEM value at the first location on the patient's skin at one or more time points before 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 measured value of a second SEM value at a second location on the patient's skin that is remote from the first location on the patient's skin.

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

[0129] Embodiment 24. The method according to Embodiment 22, wherein the second SEM value is measured substantially simultaneously with 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 disposed on a flexible substrate, the plurality of sensors being configured to measure sub-epidermal 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 being configured to control the two electrodes to detect conductive contact with the patient's skin during an SEM measurement period, and the external controller being configured to control the two electrodes to apply a therapeutic stimulus to the patient during a treatment phase.

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

[0132] Embodiment 27. The device according to embodiment 25, further comprising an adhesive layer.

[0133] Embodiment 28. The device 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 a patient in need thereof, the device comprising: two electrodes disposed on a flexible substrate such that an electric current passing between the electrodes will pass through tissue proximate to a location on the patient's skin; a sensor; and an external controller electrically connected to the two electrodes.

[0135] Embodiment 30. The integrated device according to embodiment 29, wherein the external controller is configured to control the two electrodes to detect conductive contact with the patient's skin during an SEM measurement period, and the external controller is configured to control the two electrodes to apply a therapeutic stimulus to the patient during a treatment phase.

[0136] Although the present invention has been described with reference to specific embodiments, those skilled in the art will understand that various changes may be made without departing from the scope of the present invention and that elements thereof may be replaced with equivalents. Additionally, many modifications can be made to a particular situation or material in accordance with the teachings of the present invention without departing from the scope of the present invention. Accordingly, the present invention is not limited to the specific embodiments disclosed and is intended to cover all embodiments falling within the scope and spirit of the appended claims.

Claims

1. 1. An integrated device for treating a diabetic foot ulcer in a patient in need thereof, the integrated 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 during a SEM measurement period; a first electrode and a second electrode disposed on the flexible substrate; an external controller electrically connected to the first electrode and the second electrode; an integrated device, the external controller configured to control the first electrode and the second electrode to detect contact with the patient's skin by determining a capacitance during the SEM measurement period, and the external controller configured to control the first electrode and the second electrode to apply therapeutic electrical stimulation to the patient during a treatment phase.

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

3. The integrated device of claim 1 further comprising a layer of adhesive.

4. The integrated device of claim 1 , wherein the flexible substrate is permeable to gases but impermeable to liquids.

5. The integrated device of claim 1 , wherein the therapeutic electrical stimulation is a low level voltage.

6. 10. The integrated device of claim 1, wherein the therapeutic electrical stimulation is a low level electrical current.

7. 2. The integrated device of claim 1, wherein the treatment phase includes one or more stimulation periods separated by one or more time intervals, each of the one or more stimulation periods including a duration during which the therapeutic electrical stimulation is applied, and the one or more time intervals including a duration during which the therapeutic electrical stimulation is not applied.

8. The integrated device of claim 7 , wherein each of the one or more time intervals is in the range of several hours.

9. The integrated device of claim 7 , wherein each of the one or more time intervals is in the range of several weeks.

10. The integrated device of claim 7 , wherein each of the one or more time intervals is in the range of a few hours or weeks.

11. The integrated apparatus of claim 7 , wherein the SEM measurement period is between the one or more time intervals.

12. 10. The integrated device of claim 1, further comprising a toroidal pad for relieving pressure on the patient's diabetic foot ulcer.

13. 10. The integrated device of claim 1, wherein the external controller is periodically attached to the first electrode and the second electrode during the treatment phase to apply the therapeutic electrical stimulation.

14. The integrated device of claim 1 , wherein the external controller periodically attaches to one or more of the plurality of sensors during the treatment phase to measure the SEM value.

15. 10. The integrated device of claim 1, further comprising a battery and wireless communication capabilities that enable the external controller to apply the therapeutic electrical stimulation to the patient without a wired connection to the integrated device.

16. 16. The integrated apparatus of claim 15, wherein the external controller is further enabled to communicate with the plurality of sensors and to wirelessly receive the measured SEM values.

17. 10. The integrated device of claim 1, further comprising an integrated microcontroller configured to apply the therapeutic electrical stimulation and measure the SEM value.

18. 10. The integrated apparatus of claim 1, further configured to communicate with one or more SEM applications running on one or more digital devices, the one or more digital devices being selected from the group consisting of a server, a computer, a laptop computer, and a smartphone.

19. 20. The integrated device of claim 18 configured to transfer information to and receive information from an electronic medical record (EMR).

20. 8. The integrated device of claim 7, wherein the external controller and the plurality of sensors are configured to measure tissue capacitance at respective locations on the patient's skin during the time intervals during the stimulation period.

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