HK40111804A - Measurement of susceptibility to diabetic foot ulcers - Google Patents

Description

Measurement of susceptibility to diabetic foot ulcers

This application is a divisional application of the invention application filed on February 2, 2018, with application number 201880004141.7 (international application number PCT/US2018/016741) and entitled "Measurement of Susceptibility to Diabetic Foot Ulcers".

Cross-references to related applications

This application claims priority to U.S. Provisional Application No. 62/454,482, filed February 3, 2017, and U.S. Provisional Application No. 62/521,917, filed June 19, 2017, the entire contents of which are incorporated herein by reference.

Technical Field

This disclosure provides devices and methods for assessing the feet of patients at risk of developing diabetic foot ulcers.

Background Technology

Diabetic foot ulcers require more hospitalization than any other complication of diabetes. Non-enzymatic glycosylation caused by elevated blood glucose levels leads to ligament stiffening and increased collagen cross-linking. These conditions result in damage to cell walls and blood vessels, causing an initial increase in extracellular fluid (ECF) volume. Peripheral neuropathy causes protective sensory loss and loss of muscle coordination in the foot and leg. Neuropathy increases mechanical stress in the foot during walking and standing, which, if not reduced, combined with the tissue weakness caused by diabetes, can lead to tissue death. Neuropathy also reduces a patient's ability to perceive pain, thus worsening the condition; pain is often associated with stress and tissue damage.

Each year, approximately 5% of people with diabetes develop foot ulcers, and 1% require amputation of a toe or part of the foot. In the long term, 15% of people with diabetes will develop foot ulcers, and 12-24% will require amputation. In the United States, diabetes is the leading cause of non-traumatic lower limb amputations. After the onset of foot ulcers, 20-30% of the total cost of treating diabetes is related to the treatment and healing of foot ulcers.

Current methods for preventing diabetic foot ulcers include patient education, proper foot and toenail care, appropriate footwear selection, and prompt surgical intervention. Methods for detecting pre-ulcer conditions enable the implementation of preventative measures, such as reducing the burden on the feet and improving hygiene.

Summary of the Invention

In one aspect, this disclosure provides and includes an apparatus for assessing the susceptibility of tissue to diabetic foot ulcer formation, the apparatus comprising: a plurality of electrodes embedded in a substrate, wherein a pair of electrodes is capable of forming a capacitive sensor configured to measure a first capacitance in a first tissue region near the capacitive sensor; circuitry electrically coupled to the electrodes; a processor electrically coupled to the circuitry; and a non-transitory computer-readable medium electrically coupled to the processor and including instructions stored thereon, which, when executed on the processor, perform the steps of: receiving information from the circuitry regarding a measured first capacitance from the capacitive sensor; comparing the measured first capacitance with the first reference value; and providing a signal if the amount by which the measured first capacitance differs from the first reference value is greater than a first predetermined threshold.

In one aspect, this disclosure provides and includes a method for assessing the susceptibility of tissue to the formation of diabetic foot ulcers, the method comprising: acquiring a first capacitance value at a first location on a patient's skin; acquiring 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 difference between the first capacitance value and a first reference value is greater than a first predetermined threshold and the difference between the temperature measurement and a second reference value is greater than a second predetermined threshold.

In one aspect, this disclosure provides and includes a method for assessing the susceptibility of tissue to the formation of diabetic foot ulcers, the method comprising: acquiring a first subepidermal moisture (SEM) value at a first location on a patient's skin; acquiring 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 difference between the first SEM value and a first reference value is greater than a first predetermined threshold and the difference between the temperature measurement and a second reference value is greater than a second predetermined threshold.

In one aspect, this disclosure provides and includes an integrated device for treating diabetic foot ulcers in patients in need, the device comprising: a plurality of sensors disposed on a flexible substrate, wherein the plurality of sensors are configured to measure subepidermal moisture (SEM) values at corresponding 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 SEM measurement, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

In one aspect, this disclosure provides and includes an integrated device for treating diabetic foot ulcers in patients in need, the device comprising: a sensor including two electrodes disposed on a flexible substrate such that a current passing between the electrodes will pass through tissue near the patient's skin location; and an external controller electrically connected to the two electrodes.

Attached Figure Description

Various aspects of this disclosure are described herein by way of example only with reference to the accompanying drawings. Referring now specifically to the drawings, it is emphasized that the details shown are exemplary and intended to illustrate various aspects of this disclosure. In this regard, it will be apparent to those skilled in the art how various aspects of this disclosure can be implemented by considering the description and drawings individually and together.

Figure 1A depicts the anatomical structure of the foot.

Figure 1B is an enlarged view of region A in Figure 1A.

Figure 2A depicts the initial open ulcer at time 0.

Figure 2B depicts the pressure distribution produced under the conditions shown in Figure 2A.

Figure 2C depicts the same tissue region as in Figure 2A at time 1.

Figure 2D depicts the same tissue regions in Figures 2A and 2C at time 2.

Figure 3A shows a ring-shaped bioimpedance sensor.

Figure 3B shows the idealized electric field diagram generated when the ring sensor in Figure 3A is activated.

Figure 3C shows a SEM scanner that includes the sensor shown in Figure 3A.

Figure 4 shows a first exemplary electrode array.

Figure 5 is an exemplary electrode array according to the present disclosure.

Figure 6A illustrates a first example of how the electrode array disclosed in Figure 5 can be configured to form a bioimpedance sensor according to this disclosure.

Figure 6B illustrates a first example of how the electrode array disclosed in Figure 5 can be configured to form a bioimpedance sensor according to this disclosure.

Figure 6C illustrates an example of a first sensor formed in an electrode array according to the present disclosure.

Figure 6D illustrates an example of how a second sensor can be formed to overlap with the first sensor of Figure 6C according to this disclosure.

Figure 6E illustrates an example of how a sensor, as shown in Figure 6A, is formed from an electrode array that is larger than the portion of the patient's skin that rests against the array, according to this disclosure.

Figure 6F illustrates the position of the left and right feet during SEM measurements according to this disclosure.

Figure 6G is a graph of SEM values associated with known relative positions used to identify bisymmetric positions, according to the present disclosure.

Figure 7A depicts a first example of a pad assembly incorporating multiple bioimpedance sensors according to the present disclosure.

Figure 7B depicts a second example of a pad assembly according to the present disclosure, the pad assembly including an array of electrical sensors configured such that, when in use on the pad assembly, the array of electrical sensors is located under the patient's left and right feet, respectively.

Figure 7C depicts a third example of a pad assembly according to the present disclosure, the pad assembly including one or more sensors disposed within each contour.

Figure 8A discloses a foot sleeve incorporating a bioimpedance sensor according to the present disclosure.

Figure 8B is a cross-sectional view of the foot cover of Figure 8A, showing the location of the bioimpedance sensor according to this disclosure.

Figure 9 shows a sandal incorporating a bioimpedance sensor according to the present disclosure.

Figure 10A depicts a first example structure of the addressable electrode of Figure 5, which alters sensor performance according to the present disclosure.

Figure 10B depicts a second example structure of the addressable electrode of Figure 5, which alters the sensor performance according to this disclosure.

Figure 10C depicts a third example structure of the addressable electrode of Figure 5, which alters the sensor performance according to this disclosure.

Figure 11A shows an exemplary structure of a base shaped to be positioned at a known location on a patient's skin according to the present disclosure.

Figure 11B shows a front view of the exemplary structure of Figure 11A according to this disclosure.

Figure 12 illustrates a schematic diagram of an integrated system for measuring, evaluating, storing, and transmitting SEM values according to this disclosure.

Figure 13 depicts the sensing band according to this disclosure.

Figures 14A, 14B and 14C depict an integrated sensor and stimulator assembly suitable for treating pressure ulcers according to the present disclosure.

Figure 14D depicts a bandage assembly suitable for treating pressure ulcers according to the present disclosure.

Figure 15A illustrates an exemplary method for performing SEM measurements starting from the heel, according to this disclosure.

Figure 15B illustrates an exemplary method for performing SEM measurements starting from the outer side of the heel, according to the present disclosure.

Figure 15C illustrates an exemplary method for performing SEM measurements starting from the medial side of the heel, according to this disclosure.

Detailed Implementation

This disclosure describes the measurement of various electrical properties and the derivation of SEM values indicating an increase in ECF, as well as the application of this information in the assessment of susceptibility to diabetic foot ulcers and the treatment of ulcers.

Diabetic foot ulcers are well known to occur in areas subjected to repetitive moderate loads, particularly in areas where the skeletal structure of the foot transfers weight to adjacent tissues during standing. The initial injury may occur within the tissue beneath the skin, making it undetectable visually. This initial injury releases fluid into the extracellular space, which can be detected by measuring the electrical properties of the subepidermal tissue, such as its capacitance. Monitoring extracellular fluid in hazardous areas reveals tissue deterioration, which, if left untreated, will develop into an open ulcer.

This description is not intended to be a detailed list of all different ways in which this disclosure can be implemented, or of all features that can be added to this disclosure. For example, a feature set forth with respect to one embodiment may be incorporated into other embodiments, and a feature set forth with respect to a particular embodiment may be removed from that embodiment. Therefore, this disclosure contemplates that any feature or combination of features set forth herein may be excluded or omitted in some embodiments of this disclosure. Furthermore, many variations and additions to the various embodiments proposed herein will be apparent to those skilled in the art and do not depart from this disclosure. In other instances, well-known structures, interfaces, and processes have not been shown in detail so as not to unnecessarily obscure the invention. Nothing in this specification should be construed as denying any part of the full scope of the invention. Therefore, the following description is intended to illustrate some specific embodiments of this disclosure, rather than exhaustively specifying all substitutions, combinations, and variations thereof.

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 pertains. The terminology used in the description of this disclosure is for the purpose of describing particular aspects or embodiments only and is not intended to be limiting of this disclosure.

All publications, patent applications, patents, and other references cited herein are incorporated in their entirety into the teachings relating to the sentence and/or paragraph in which they appear. References to techniques used herein are intended to refer to techniques commonly understood in the art, including variations of those techniques or substitutions for equivalent techniques that are obvious to those skilled in the art.

U.S. Patent Application Serial No. 14/827,375 discloses a device for measuring subepidermal capacitance using radio frequency (RF) energy via a bipolar sensor similar to sensor 90 shown in Figure 3A, wherein the subepidermal capacitance corresponds to the water content of a target area of a patient's skin. Application '375 also discloses arrays of these bipolar sensors of different sizes.

U.S. Patent Application Serial No. 15/134,110 discloses a device similar to the one shown in Figure 3C for measuring subepidermal moisture (SEM), wherein the device transmits and receives a radio frequency signal at a frequency of 32 kHz via a single coaxial sensor and generates a bioimpedance signal, which is then converted into an SEM value.

The entire contents of U.S. Patent Application Serial Nos. 14/827,375 and 15/134,110 are incorporated herein by reference.

Unless the context otherwise requires, the various features of this disclosure described herein can be used explicitly in any combination. Furthermore, this disclosure is also contemplated that in some embodiments thereof, any features or combinations of features set forth herein may be excluded or omitted.

The methods disclosed herein include one or more steps or actions for implementing the methods. The method steps and/or actions may be interchanged without departing from the scope of the invention. In other words, unless the correct operation of an embodiment requires a specific order of steps or actions, the order and/or use of specific steps and/or actions may be modified without departing from the scope of the invention.

As used in the description of this disclosure and the appended claims, the singular forms “a”, “an”, and “the” are also intended to include the plural forms, unless the context clearly indicates otherwise.

As used herein, “and/or” means and includes any and all possible combinations of one or more of the associated listed items, and excludes combinations when interpreted in an alternative manner (“or”).

As used herein, the terms “approximately” and “approximately” are intended to include variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or even ±0.1% when referring to measurable values (such as length, frequency, or SEM values).

As used herein, phrases such as “between X and Y” and “between approximately X and Y” should be interpreted as including both X and Y. As used herein, phrases such as “between approximately X and Y” mean “between approximately X and approximately Y”, while phrases such as “from approximately X to Y” mean “from approximately X to approximately Y”.

As used in this article, the term "subepidermal moisture" or "SEM" refers to the increase in tissue fluid and localized edema caused by vascular leakage and other changes that alter the basic structure of damaged tissue under conditions of sustained tissue pressure, apoptosis, necrosis, and inflammation.

As used herein, a “system” can be a collection of devices that are connected to each other by wired or wireless communication.

As used in this article, “inquiry” refers to the use of radiofrequency energy to penetrate the patient’s skin.

As used in this article, "patient" can be a human subject or an animal.

As used in this article, “healthy” can be used to describe tissues that do not show symptoms of cell wall or blood vessel damage, where an increase in the amount of ECF is an indicator of such damage.

As used herein, “extracellular fluid” or “ECF” refers to body fluids contained outside cells, including plasma, interstitial fluid, and transcellular fluid.

As used in this article, “prone to diabetic foot ulceration” can be used to describe tissues exhibiting symptoms of cell wall or vascular damage, such as edema or increased ECF levels, but without open ulcers.

As used in this article, "time 0" refers to the initial time point, such as the time when an open ulcer is first detected.

As used in this article, "time 1" refers to a time point later than time 0.

As used in this article, "Time 2" refers to a time point later than Time 1.

Figure 1A is a side view of a portion of the anatomical structure of the foot 20. The areas of the foot most likely to develop diabetic foot ulcers are the heel below the calcaneus 21 and the ball of the foot below the metatarsals 22.

Figure 1B is an enlarged view of region “A” in Figure 1A. The ends of the metatarsals 22 and adjacent phalanges 23 are shown as skin 24 near the sole of the foot 20. A portion of the patient’s body weight generates a compressive force 30 exerted by the metatarsals 22 on the tissues in region 40. Force 30 is resisted by resistance 36 exerted by the floor on the skin 24 beneath region 40 to support the patient. The patient’s muscle activity, such as simply balancing on the feet when walking or standing, generates a shear force 32 between the metatarsals 22 and the tissues 40, and a resisting shear force 38 between the floor and the skin 24. Thus, the tissues in region 40 are subjected to both compressive and shear forces simultaneously.

It has been observed that healthy patients, when standing still, shift their weight from one foot to the other and move their center of mass relative to their feet. This limits the duration for which force is applied to any particular tissue area. However, peripheral neuropathy reduces the sensation of body weight in the tissues, thus reducing the unconscious shifting of their weight, and a lack of normal movement has been observed in patients with peripheral neuropathy when standing. This results in prolonged application of sustained compressive force to localized areas of tissue (such as area 40). Such prolonged exposure to moderate-intensity pressure is thought to lead to ulceration in these areas.

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

Figure 2B depicts the pressure distribution under the conditions of Figure 2A. The force exerted by the floor or the patient's shoes is applied as a localized uniform pressure 56 to the skin 24 of the foot 20. The applied pressure 56 is resisted internally by a force 53. Because the tissue has sloughed off, no pressure can be applied to the ulcer 50. Therefore, the internal force in the annular region 52A increases to a peak 54 to absorb the force that should have been applied to the ulcer 50. This peak force 54 is large enough to cause further tissue damage in the annulus 52A. As the body attempts to protect itself from the increased pressure, a callus typically forms on region 52A. However, the tissue beneath the callus is still damaged and will exhibit an increase in ECF.

Figure 2C depicts the same tissue area at time 1, following time 0. The increased pressure level in region 52A caused tissue death in region 52A, and tissue in region 52B sloughed off, making ulcer 50B larger than the previous ulcer 50A. However, the applied pressure 56 remained unchanged, so the tissue in region 52B surrounding the larger ulcer 50B now had to receive more force. This accelerated the expansion of ulcer 50, as the tissue in region 52B died faster under the higher applied load.

Figure 2D depicts the same tissue area as Figures 2A and 2C at time 2, following time 1. Ulcer 50 grows to size 50C, and the area 52C with increased pressure is larger than the previous areas 52A and 52B.

In the case of an already formed ulcer, as shown in Figure 2A, interventional treatment will be introduced to prevent the growth of ulcer 50 and allow the body to heal the open ulcer 50. Treatment may include placing a pressure-reducing pad around the ulcer to diffuse pressure 56 to a larger area of healthy tissue and eliminate peaks 54 that could lead to further damage. However, the effectiveness of the treatment can only be determined by observing whether the ulcer develops further over time.

Figure 3A discloses a ring-shaped bioimpedance sensor. In this exemplary structure, a central electrode 110 is surrounded by a ring electrode 120. Without being limited to a specific theory, the gap between the two electrodes affects the electric field penetration depth of the substrate beneath the sensor 90. In one aspect, a ground plane (not visible in Figure 3A) is parallel to and separate from the electrode planes, while in another aspect, it extends beyond the outer diameter of the ring electrode 120. Without being limited to a specific theory, the ground plane can confine the electric field between electrodes 110 and 120 to one side of the planes of electrodes 110 and 120, said side being located on the side of the planes of electrodes 110 and 120 opposite to the ground plane.

Figure 3B illustrates an idealized electric field diagram generated when the annular sensor of Figure 3A is activated by a driving circuit (not shown in Figure 3B). When a voltage is applied across electrodes 110 and 120, an electric field 140 is generated between electrodes 110 and 120, extending outward from the plane of electrodes 110 and 120 to a field depth 150. The diameter of the central electrode 110, the inner and outer diameters of the annular electrode 120, and the gap between electrodes 110 and 120 can be varied to alter the characteristics of the electric field 140, such as the field depth 150.

In use, the drive circuit can measure electrical characteristics or parameters, including one or more electrical characteristics selected from the group consisting of resistance, capacitance, inductance, impedance, magnetoresistive properties, and other electrical characteristics sensed by the 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 capacitive 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 certain depth, determined by the geometry 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 another aspect, the measured moisture content corresponds to SEM content, with values within a predetermined range. In one aspect, the predetermined scale can be from 0 to 20, for example, from 0 to 1, from 0 to 2, from 0 to 3, from 0 to 4, from 0 to 5, from 0 to 6, from 0 to 7, from 0 to 8, from 0 to 9, from 0 to 10, from 0 to 11, from 0 to 12, from 0 to 13, from 0 to 14, from 0 to 15, from 0 to 16, from 0 to 17, from 0 to 18, from 0 to 19. In one aspect, the predetermined scale can be scaled by a factor or multiple based on the values provided herein. In one aspect, multiple measurements are performed while varying one or more of these operating characteristics between readings, thereby providing information related to the moisture content at different depths of the skin.

One or more body parts can be defined on the body. In one aspect, measurements taken within a body part are considered comparable. A body part can be defined as an area on the skin of the body, where measurements can be taken at any point within that area. In one aspect, a body part corresponds to an anatomical body part (e.g., heel, ankle, lower back). In one aspect, a body part can be defined as a set of two or more specific points relative to an anatomical feature, where measurements are taken only at those specific points. In one aspect, a body part can include multiple discontinuous areas on the body. In one aspect, the set of specific locations can include points within multiple discontinuous areas.

In one respect, the location is defined by surface area. In one respect, the location may be, for example, between 5 and 200 ^cm² , between 5 and 100 ^cm² , between 5 and 50 ^cm² , or between 10 and 50 ^cm² , between 10 and 25 ^cm² , or between 5 and 25 ^cm² .

In one aspect, measurements can be taken using a specific pattern or a portion thereof. In another aspect, the pattern for readings is created within a pattern having a relevant target area at its center. In another aspect, measurements are taken on tissues or sites using one or more circular patterns of increased or decreased size, T-shaped patterns, a set of specific locations, or randomly. In another aspect, a pattern can be positioned on the body by defining a first measurement position of the pattern relative to an anatomical feature, with the remaining measurement positions of the pattern defined as offsets from the first measurement position.

In one aspect, multiple measurements are performed on a tissue or site, and the difference between the lowest and highest measurements from the multiple measurements is recorded as the delta value of the multiple measurements. In another aspect, 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 performed on the tissue or site.

In one aspect, a threshold may be established for at least one site. In another aspect, a threshold of 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or other values may be established for the at least one site. In one aspect, a delta value is identified as significant when the delta values of multiple measurements performed within a site meet or exceed a threshold associated with that region. In one aspect, each of the multiple sites has a different threshold. In one aspect, two or more sites may share a common threshold.

In one aspect, the threshold has both a delta value component and a time component, wherein a delta value is identified as significant when it is greater than a predetermined value and persists for a predetermined portion of a time interval. In another aspect, the predetermined portion of the time interval is defined as a minimum of X days, wherein multiple measurements taken during these days produce a delta value greater than or equal to the predetermined value over a total of Y consecutive measurement days. In another aspect, the predetermined portion of the time interval can be defined as 1, 3, 4, or 5 consecutive days, during which multiple measurements produce a delta value greater than or equal to the predetermined value. In yet another aspect, the predetermined portion of the time interval can be defined as a portion of different specific time periods (week, month, hour, etc.).

In one aspect, the threshold has a trend aspect, where changes in delta values measured multiple times consecutively are compared with each other. In another aspect, the trend threshold is defined as a predetermined change in the delta value over a predetermined time length, where it is important to determine whether the threshold is met or exceeded. In another aspect, the determination of significance leads to the issuance of an alarm. In another aspect, the trend line can be calculated based on a portion of a single measurement from multiple consecutive measurements. In another aspect, the trend line can be calculated based on a portion of the delta values from multiple consecutive measurements.

In one aspect, the number of measurements performed within a single site may be less than the number of measurement locations defined in the pattern. In another aspect, after a predetermined initial number of readings has been performed in a site, fewer than the number of measurement locations defined in the pattern, and after each additional reading in the same site, a delta value is calculated, wherein no additional readings are performed once the delta value reaches or exceeds a threshold associated with that site.

In one respect, the number of measurements taken within a single location can exceed the number of measurement locations defined in the pattern. In another respect, the delta value will be calculated after each additional reading.

In one aspect, a quality metric can be generated for each multiple measurement. In one aspect, the quality metric is selected to assess the repeatability of the measurement. In one aspect, the quality metric is selected to assess the skill of the clinician performing the measurement. In one aspect, the quality metric may include one or more statistical parameters, such as mean, standard deviation, or mean value. In one aspect, the quality metric may include one or more comparisons of a single measurement value to a predetermined range. In one aspect, the quality metric may include comparing a single measurement value to a pattern of values, such as comparing a measurement value at a predetermined location to a range associated with each predetermined location. In one aspect, the quality metric may include determining which measurements are performed on healthy tissue and one or more assessments of consistency within that subset of “healthy” measurements, such as range, standard deviation, or other parameters.

In one respect, the measured value, such as the threshold, is determined by a SEM scanner model 200 (Bruin Biometrics, Los Angeles, California). In another respect, the measured value is determined by another SEM scanner.

In one aspect, the measurements are based on capacitance measurements performed using a reference device. In another aspect, the capacitance measurements can depend on the location of any electrodes in the device and other factors. This variation can be compared to a reference SEM device, such as the SEM scanner Model 200 (Bruin Biometrics, Los Angeles, California). Those skilled in the art will understand that the measurements presented herein can be adjusted to accommodate different capacitance ranges by referring to a reference device.

Figure 3C provides top and bottom views of a SEM scanner 170, which includes electronics that drive a sensor 174, similar to sensor 90 in Figure 3A. The electronics also measure the capacitance between electrodes 110 and 120. This capacitance can be converted into an SEM value displayed on a display 176.

Various aspects of the sensor 90 and the SEM scanner 170 are disclosed in WO 2016/172263, and U.S. Patent Application Serial No. 15/134,110 was filed as an application entering the national phase, all of which are incorporated herein by reference in their entirety.

Figure 4 depicts an exemplary electrode array 290 according to the present disclosure. Array 290 consists of individual electrodes 300, which in this example are arranged in a regular pattern on a substrate 292. In one aspect, each electrode 300 is coupled (via a conductive element not shown in Figure 4) to a circuit (not shown in Figure 4) configured to measure electrical parameters. In one aspect, a “virtual sensor” is created by selectively connecting 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 in Figure 3A, and six electrodes 320A-320F are connected together as a “virtual ring” electrode, similar to electrode 120 in Figure 3A. In one aspect, two separate electrodes are individually connected to the circuit to form a virtual sensor, for example, electrodes 310 and 320A are connected as two electrodes of the sensor, respectively. In one aspect, one or more electrodes 300 are connected together to form one or the other electrode of a dual-electrode sensor.

Any pair of electrodes, whether consisting of a single electrode or a group of electrodes coupled together to form a dummy 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, magnetoresistive force, or other electrical characteristics, using one or more of sensors 90, 174, 290, 430, 440, or other dual-electrode sensors. The electronic device of this disclosure can be further configured to compare a measured first capacitance with a reference value, and to provide a signal if the difference between the measured capacitance and the reference value is greater than a threshold value. In one aspect, one or both of the reference value and the threshold value are predetermined.

Figure 5 depicts another exemplary array 400 of electrodes 410 according to the present disclosure. In this non-limiting example, each electrode 410 is approximately hexagonal, separated from each surrounding electrode 410 by a gap 420. In one aspect, the electrodes 410 are one of circular, square, pentagonal, or other regular or irregular shapes. In one aspect, the gap 420 is uniform among all electrodes 410. In one aspect, the gap 420 varies among different electrodes. In one aspect, the gap 420 has a width 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.

Figure 6A depicts an array 400 of electrodes 410 according to the present disclosure, configured, for example, to be connected to a measurement circuit to form an exemplary sensor 430. A single hexagonal electrode 410 marked "1" forms a center electrode, and a ring of electrodes 410 marked "2" interconnects to form a ring electrode. In one aspect, the electrode 410 between the center electrode and the ring electrode is electrically "floating". In another aspect, the electrode 410 between the center electrode and the ring electrode is grounded or connected to a floating ground. In one aspect, the electrode 410 outside the ring electrode is electrically "floating". In another aspect, the electrode 410 outside the dummy ring electrode is grounded or connected to a floating ground.

Figure 6B depicts an alternative aspect according to the present disclosure, wherein an array 400 of electrodes 410 has been configured to form a virtual sensor 440. In one aspect, a plurality of electrodes 410, indicated by "1", are interconnected to form a central electrode, while a ring of electrodes, indicated by "2", is interconnected to form a ring electrode. In another aspect, electrodes 410 of various numbers and positions are interconnected to form virtual electrodes of various sizes and shapes.

Figures 6A and 6B depict an exemplary structure of an electrode array 400 capable of forming a sensor 430 at multiple overlapping locations according to the present disclosure. In Figure 6A, a virtual sensor 430A is formed having a central electrode 432 (represented by "1") formed by a single electrode 410 and a ring electrode 434 (represented by "2") formed by multiple electrodes 410. The same array 400 is shown in Figure 6B, wherein a new virtual sensor 430B is formed having a central electrode 436 (represented by "3") and a ring electrode 438 (represented by "4"). The location of the virtual sensor 430A is shown by black outline. It can be seen that the location of the virtual sensor 430B overlaps with that of the virtual sensor 430A, thereby allowing measurements to be performed at a finer resolution than the diameter of the sensor 430.

Figure 6E illustrates how, according to this disclosure, sensor 430 is formed from electrode array 400, which is larger than the portion of the patient's skin that abuts against the array. In this example, viewed from below the foot, the outline of the contact area 450 of the sole 22R of the patient's right foot is shown as covering the array 400. In this example, sensor 430C has been formed at a location where a portion of sensor 430C extends beyond the edge of the contact area 450. At this location, the capacitance or other electrical parameters measured by sensor 430C are lower than the capacitance measured by sensor 430D, which is entirely located within the contact area 450. It can be seen that sensor 430 can be formed at any point within the array 400 and, depending on the position of sensor 430, can partially overlap the contact area at any level within the range of 0-100%.

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 another 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 respect, 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%.

In one aspect, the sensor array 400 may further include a plurality of contact sensors (not shown in FIG. 6E) that are on the same flat surface and surround the electrode to ensure that one or more virtual sensors are in full contact with 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 ultrasound sensors, a plurality of bone growth stimulator sensors, or a plurality of combinations of these sensors. In some embodiments, the plurality of contact sensors may include four, five, six, seven, eight, nine, or ten or more contact sensors surrounding each electrode.

Figures 6F and 6G depict an example of how a comparison of SEM values associated with sensors in known relative positions, according to this disclosure, identifies bisymmetrical positions. In this example, non-overlapping positions where sensor 430 is formed on the contact area 450R of the right foot 20R are labeled “A” to “H” in Figure 6F. The SEM values measured at each position are plotted in the graph of Figure 6G. In this example, the SEM values at positions “A” and “H” are low or zero, indicating that sensor 430 does not overlap with the contact area 450 at these positions. The SEM values associated with positions “B” and “G” are higher because sensor 430 overlaps with a portion of the contact area 450 at these positions. The SEM values at positions C-D-E-F are higher, and in this example, approximately the same, indicating that sensor 430 is completely within the contact area 450 at these positions. In one aspect, SEM measuring devices such as device 180 can determine that certain positions, such as positions “C” and “F”, are bisymmetrical relative to the centerline 452R of the right foot 20R. In one respect, a similar set of measurements at positions A'-H' on the left foot 20L, and positions on feet 20L and 20R, such as positions E and E', can be determined to be approximately bisymmetric.

Figure 7A depicts an exemplary pad assembly 500 incorporating multiple bioimpedance sensors 520 according to the present disclosure. Although the sensors 520 are shown as annular sensors similar to sensor 90 shown in Figure 3A, the sensors 520 can be any structure of an electrical measurement sensor, including the structures shown in Figures 4, 5, and 6A-6B. The sensors 520 are distributed on a substrate 510. In one aspect, a portion of the substrate 510 is flexible. In another aspect, a portion of the substrate 510 is rigid. In one aspect, the electrodes of the sensors 520 are electrically exposed, so that they can make conductive contact with the patient's foot when the patient stands on the pad assembly 500. In another aspect, the electrodes of the sensors 520 are electrically insulated, for example through an insulating overlay (not shown in Figure 7A), so that they make capacitive electrical contact only with the patient's foot when the patient stands on the pad assembly 500.

In one aspect, the pad 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 another aspect, the temperature sensors are located in the same location as the SEM sensor 520 for temperature and SEM measurements at a common location.

In one aspect of the pad assembly 500, a signal is provided when the difference between the measured capacitance and a reference capacitance value is greater than a first threshold and the difference between the measured temperature and a temperature reference value is greater than a second threshold. In one aspect, one or both thresholds are predetermined. In one aspect, the first threshold is set at the corresponding reference capacitance value plus at least 5%, such as at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500%. In one aspect, the second threshold is set at 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 another aspect, one or both of the capacitance and temperature reference values are determined by previous measurements, such as a moving average of the past five consecutive measurements, or by the average of multiple measurements taken in an earlier time period, such as one month ago.

In one respect, one or both of the capacitance and temperature reference values are determined from measurements taken when the tissue is in a known healthy state, such as measurements taken in a doctor's office when a clinician examines the tissue and determines that it is healthy and not prone to forming diabetic foot ulcers.

Figure 7B depicts another exemplary pad assembly 502, which includes arrays 530L and 530R of electrical sensors 520, wherein arrays 530L and 530R are configured to be positioned under the left and right feet of the patient, respectively, when on the pad assembly 502. In one aspect, the outlines 540L and 540R of the left and right feet are drawn on arrays 530L and 530R to guide the patient to stand in the appropriate position.

Figure 7C depicts one aspect of a pad assembly 504 having one or more sensors 520 disposed within each of contours 540L and 540R. In one aspect, sensor 520A is located at a position corresponding to the part of the foot most likely to form an ulcer, such as the metatarsal ball. In another aspect, sensor 520B may be located under the heel or other location of the foot.

In one aspect, the substrate 510 is partially transparent, and the pad 504 includes a second substrate 512 on which one or more optical sensors 550 are mounted. In one aspect, the optical sensor 550 is a camera capable of imaging the lower side of a patient's foot standing on the pad 504. In one aspect, the optical sensor 550 is sensitive to visible light. In one aspect, the optical sensor 550 is sensitive to infrared light.

Patients can periodically use pad assemblies 500, 502, 504, etc., to monitor changes in foot health. For example, a baseline is established by a clinician measuring the electrical properties (such as capacitance) of each foot during an examination, confirming the absence of ulcers or signs of lesions that could lead to ulceration. The patient then places pads 500, 502, 504 in an easily accessible location at home, such as in front of the bathroom sink. Periodically, such as while brushing teeth daily, the patient triggers measurements of the feet via sensor 520. If the patient stands in the same location, for example guided by contours 540L and 540R, each sensor 520 and 550 measures the same location in each repeated measurement. In one aspect, temperature measurements are taken by infrared sensor 550 or one or more temperature sensors in pad assemblies 500, 502, 504 (not shown in Figure 7C). In another aspect, images are captured by optical sensor 550 in pad assembly 504. This information is stored in local memory or transmitted to a remote storage location, such as a doctor's office. Daily measurements are compared to reference values derived from previous measurements (e.g., measurements taken in the clinician's office or the average of measurements from the previous week). If a recent measurement deviates from the reference value, the patient is informed of the deviation. The patient can then consult their clinician for further evaluation and possible interventions. In one aspect, a change in SEM value measured above a threshold triggers a notification. In another aspect, a change in SEM value measured above a first threshold and a change in temperature measured above a second threshold together trigger a notification. In yet another aspect, a change in SEM value measured above the first threshold or a change in temperature measured above the second threshold triggers a notification. In one aspect, the first threshold is set at the corresponding reference SEM 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 aspect, the second threshold is set at 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 another aspect, information such as images of the patient's lower foot is always sent to the clinician for examination.

In one aspect, the measurements of the left and right feet are compared. For example, referring to Figures 6F and 6G, positions E and E' are compared. In another aspect, 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.

Figure 8A illustrates a foot cover 600 incorporating a bioimpedance sensor 520 as shown in the cross-sectional view of Figure 8B, according to the present disclosure. In one aspect, the foot cover 600 includes a sock or other flexible, suitable garment 610 into which the foot can be inserted. In one aspect, the flexible, suitable garment 610 may be a flexible shoe similar to a "water shoe," made of a flexible, elastic material such as rubber. In one aspect, the flexible, suitable garment 610 may be a conventional shoe, such as leather dress shoes or athletic shoes. The sensor 520 is located at one or more locations corresponding to the danger zone for ulcer formation. In one aspect, the sensor 520 is located below or around the heel of the flexible, suitable garment 610. In one aspect, the sensor 520 is located on the sole portion of the flexible, suitable garment 610. In one aspect, the sensor 520 is located in the area around the toes of the flexible, suitable garment 610 (not visible in Figure 8B).

Figure 9 illustrates a sandal 650 incorporating a bioimpedance sensor 520 according to the present disclosure. One or more sensors 520 are disposed on the sandal at locations corresponding to potential ulcer formation areas.

Figures 10A, 10B, and 10C depict the structure of the addressable electrode of Figure 5, which alters sensor performance according to the present disclosure. Figure 10A depicts an exemplary first structure 700, in which electrodes 710 are connected to form a central electrode 720 and a ring electrode 730, similar to the electrodes of Figures 6A and 6B. Referring to Figure 3B, the sensor structure 700 has a gap 740 between the single row of electrodes 710, which creates a first electric field depth 150.

Figure 10B depicts a second exemplary structure 702 of the same sensor array 710, in which one electrode is connected to form a central electrode 722, while multiple electrodes 710 are connected to form a ring electrode 732 with a diameter larger than that of the ring electrode 730 and a gap 742 larger than that of the gap 740. The sensor structure 702 will have a second electric field depth 150 greater than that of the sensor structure 700.

Figure 10C depicts a third exemplary structure 704 of the same sensor array 710, in which one electrode is connected to form a central electrode 724, while multiple electrodes 710 are connected to form an annular electrode 734 with a diameter greater than that of the ring electrodes 730 and 732 and a gap 744 greater than that between the gaps 740 and 742. Sensor structure 704 will have a third electric field depth 150 greater than that of either sensor structure 700 or 702.

In one aspect, the pad assembly 500 includes an electrode array 710 distributed on a portion of a base 510. At array locations corresponding to danger zones in the patient's foot, the pad assembly 500 is configured to form a sensor structure 700 and perform a first measurement, then the electrodes 710 are reconfigured to form a sensor structure 702 and perform a second measurement. The first and second measurements provide information about ECF differences at different depths beneath the skin of the foot, thereby enabling a better understanding of the internal tissue condition of the foot. In another aspect, the pad assembly 500 is subsequently configured to form a sensor structure 704 and perform a third measurement. Comparison of the three measurements achieves higher resolution of the internal tissue condition.

Figures 11A and 11B depict exemplary aspects of a sensor assembly 500 configured to be placed at a known location on a patient's skin according to the present disclosure. In this example, the sensor assembly 500 has a shaped substrate 510 configured to conform to the posterior and subsurface surfaces of the heel of the foot 20. In one aspect, the shaped substrate 510 is suitable for 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 shaped substrate 510. In this example, the sensors 520 are configured as annular sensors, as shown in Figure 1A. In one aspect, referring to Figure 5, the inner surface of the shaped substrate 510 is lined with an array 400 of electrodes 410, allowing virtual sensors to be formed at any location. In one aspect, sensors of other shapes and structures are disposed on the inner surface of the shaped substrate 510. In one aspect, the shaped substrate 510 is a flexible panel (not shown in Figure 11A) that can conform to the patient's skin, for example, wrapped around the back of the ankle. In one aspect, sensor assembly 500 includes cable 530 for connecting sensor 520 to one or more of a power source, circuitry configured to measure one or more of capacitance or other electrical characteristics, processor, communication subsystem, or other type of electronic component (not shown in FIG11A).

Figure 11B depicts an exemplary structure of the sensor assembly 500, wherein a plurality of sensors 520 are disposed on a molding substrate 510 such that, for example, the sensor assembly 500 is placed against the patient's skin around the back, sides, and bottom of the center of the right heel. This enables multiple SEM measurements at repeatable locations on the heel, with the sensor assembly 500 in a single location. In one aspect (not shown in Figures 11A and 11B), the sensor assembly 500 is configured to be placed on a portion of the patient's back, thereby enabling measurements at bi-symmetrical locations on the back. In one aspect, the molding substrate 510 is configured to match the anatomical features of a target area of the patient. In one aspect, the molding substrate 510 includes markers or other indicators that can be aligned with features of the patient's body to enable measurements to be taken intermittently at the same location over a period of time generally ranging from hours to weeks. In one aspect, the sensor assembly 500 is integrated into a clothing lining or shoe or other garment. In one aspect, the sensor assembly 500 is integrated into a sheet, blanket, padding, or other type of bedding. In one aspect, sensor assembly 500 has wireless communication capabilities, such as passive RFID or inductive coupling, to enable the driving of sensor 520 without physical connection to sensor assembly 500.

In one aspect, sensor 520 is coupled to electronics (not shown in FIG11B) configured to compare a current set of measurements with each other and with previous measurements at the same location. In another aspect, the electronics of this disclosure can provide a signal if one or more of certain conditions are met. Such conditions may include, but are not limited to, the change in the difference between measurements at two identical locations compared to the difference between measurements at two previous locations, and the change in the measurement at a particular location relative to a previous measurement at the same location being greater than a threshold.

Figure 12 illustrates a schematic diagram of an integrated system 800 for measuring, evaluating, storing, and transmitting SEM values according to the present disclosure. In this example, system 800 includes an SEM measurement device 810, such as an SEM scanner 170, which has the capability to wirelessly communicate with a WiFi access point 820. Device 810 communicates with one or more of an SEM application running on server 850 and applications running on a laptop computer 840, a smartphone 830, or other digital devices. In one aspect, the laptop computer 840 and smartphone 830 are carried by a user of device 810, such as a nurse, and the applications provide feedback and information to the user. In one aspect, patient information received from device 810 is stored in database 850. In one aspect, patient information received from device 810 is stored in database 860. In one aspect, information received from device 810 is transferred via network 855 to another server 880, which stores a portion of the information in the patient's electronic medical record (EMR) 870. In one aspect, information retrieved from device 810 or from database 860 or EMR 870 is transferred to external server 890 and then to computer 895, such as the computer in the office of a doctor examining and caring for a patient.

In one aspect, device 810 is one of pad assembly 500, foot cover 600 or other measuring devices, and the patient uses one or both of smartphone 830 and laptop computer 840 to receive information and notifications related to measurements performed by pad assembly 500.

Figure 13 depicts a sensing band 550 according to the present disclosure. In one aspect, a SEM sensor, such as sensor 90 or sensor 400 as described herein, is embedded in band 554, which may be wrapped around the lower leg 60 as shown in Figure 13. In one aspect, band 554 includes sensors configured to measure one or more oxygenations of tissue, which may include measurements of one or both of oxyhemoglobin and deoxyhemoglobin, temperature, pulse rate, blood volume, and blood pressure at one or more points on the skin. In one aspect, a combination of measurements performed by band 554 provides information about blood flow to the foot, where reduced blood flow is a possible indication of DFU formation. In one aspect, this information includes measurements of blood volume and refill time in the portion of the lower leg 60 adjacent to band 554.

Figure 14A depicts an integrated sensor and stimulator assembly 201 suitable for treating pressure ulcers according to the present disclosure. In one aspect, the integrated sensor and stimulator assembly 201 is provided to a patient in need. 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 indication of tissue health at the location of the respective sensor 90. In one aspect, when the assembly 201 is placed on the skin, two electrodes 212A and 212B are in conductive contact with the patient's skin (not shown in Figure 14A). 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 for a duration having a time period and a time interval between the time periods. In one aspect, a low-level voltage and/or current can aid in 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 aspect, capacitance is measured over time intervals between stimulation periods. In another aspect, the time interval can generally range from several hours to several weeks. In one aspect, component 201 includes an absorbent pad and a non-adhesive layer (not shown in FIG. 14A) covering sensor 90 and electrodes 212A, 212B. In one aspect, component 201 includes an adhesive layer (not shown in FIG. 14A) covering a portion of substrate 210, thereby allowing component 201 to adhere to the patient's skin. In one aspect, substrate 201 may be gas-permeable but impermeable to fluids.

The combination of a standard bandage (absorbent pad, non-adhesive layer, and covering base) with treatment instruments (such as electrodes 212A, 212B and associated external controllers) and one or more sensors 90 provides a means to protect the wound, improve the healing process, and monitor healing without interfering with component 201.

Figure 14B depicts the sole of the foot of a patient with pressure ulcer 205.

Figure 14C depicts a component 201 adhered to the sole of the foot 20 over a pressure ulcer 205. In one aspect, component 201 is placed over the pressure ulcer 205 and left in place for several days. In another aspect, component 201 includes an annular pad that relieves pressure on the 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, external controllers for sensors 90 are attached to one or more of sensors 90 to perform SEM measurements.

In one aspect, component 201 includes a battery and wireless communication capabilities, enabling an external controller to apply stimulation via electrodes 212A, 212B without a wired connection to the component. Similarly, the component can be configured to allow an external controller to communicate with sensor 90 to perform and receive SEM measurements without a wired connection. In another aspect, component 201 includes a microcontroller configured to apply therapeutic stimulation, perform SEM measurements, and wirelessly transmit information such as SEM values.

It will be apparent to those skilled in the art that the concept of combining therapeutic instruments with SEM sensors can be applied to other types of wounds and other parts of the body besides the sole of the foot, such as the ankle or bony prominences.

Figure 14D depicts a bandage assembly 202 adapted for placement over a pressure ulcer on the sacrum of a patient in need. Assembly 202 includes a base 220 that is gas-permeable but fluid-impermeable. Assembly 202 includes a pad 222 (viewed from the outside of Figure 14D) that provides both protection and absorption. In this example, a single sensor 90 is located under the pad 222 such that when the assembly is applied to an early pressure ulcer with unbroken skin, the sensor is directly above the pressure ulcer. Electrodes 214A and 214B are located near the sensor 90 and on the same underside, thus making contact with the patient's skin. In this configuration, assembly 202 can be placed over an early ulcer and protect, improve the healing process, and monitor healing progress as assembly 202 is removed or the wound is disturbed.

The invention has now been generally described, and will be more readily understood by referring to the following examples. These examples are provided by way of illustration and are not intended to limit the disclosure unless specifically stated otherwise.

Example

Example 1: SEM measurements at multiple locations on the foot

Use one of the following three methods to perform SEM measurements on the foot to ensure that the electrode is in full contact with the human patient's skin.

Figure 15A illustrates a method for performing SEM measurements starting from the heel using the apparatus according to this disclosure. First, the forefoot is dorsiflexed so that the toes point towards the tibia. Next, the bioimpedance sensor 1520 is placed at the bottom of the heel 1530. The electrodes are adjusted to make full contact with the heel, and then multiple SEM measurements are performed along a straight line for all 10 toes (including the metatarsal balls 1540). The metatarsal balls are one of the main sites of diabetic foot ulcers.

Figure 15B illustrates a method for performing SEM measurements starting from the lateral aspect of the heel using the apparatus according to this disclosure. First, the toes are pointed away from the body and rotated inward toward the body. Second, electrodes are placed on the side of the heel 1550. The bioimpedance sensor 1520 is adjusted to be in full contact with the heel, and multiple SEM measurements are performed in a straight line toward the sole. The metatarsal ball 1540 is also shown in Figure 15B.

Figure 15C illustrates a method for performing SEM measurements starting from the inner side of the heel using the apparatus according to this disclosure. First, the toes are moved away from the body and rotated to one side. Second, electrodes are placed on the inner side of the heel 1560. The bioimpedance sensor 1520 is adjusted to be in full contact with the heel, and multiple measurements are taken in a curved pattern around the back of the heel.

As can be seen from the above, the present invention can be implemented in various ways, including but not limited to the following:

Example 1. An apparatus for assessing tissue susceptibility to diabetic foot ulcer formation, the apparatus comprising: a plurality of electrodes embedded in a substrate, wherein a pair of the electrodes is capable of forming a capacitive sensor, the capacitive sensor being configured to measure a first capacitance in a first tissue region near the capacitive 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 including instructions stored thereon, the instructions, when executed on the processor, performing the following steps: receiving information from the drive circuit regarding the measured first capacitance; comparing the measured first capacitance with the first reference value; and providing a signal if the difference between the measured first capacitance and the first reference value is greater than a first predetermined threshold.

Example 2. The apparatus according to Example 1, wherein the first reference value is predetermined.

Example 3. The apparatus according to Example 1, wherein the first reference value is determined by measuring the first capacitance when the first tissue region is healthy.

Example 4. The apparatus according to Example 1, wherein the first reference value is determined by measuring the first capacitance at the first tissue region once or multiple times prior to the most recent measurement of the first capacitance.

Example 5. The apparatus according to Example 1, wherein the first reference value is determined by measurements of the bisymmetrical positions.

Example 6. The apparatus according to Example 1, wherein the first reference value is a measurement of the second capacitance of a second tissue region separated from the first tissue region.

Example 7. The apparatus according to Example 6, wherein the second tissue region is known to be healthy.

Example 8. The apparatus according to Example 6, wherein the second capacitor is measured almost simultaneously with the first capacitor.

Example 9. The apparatus according to Example 1, the apparatus further comprising one or more temperature sensors configured to measure the temperature of the first tissue region and coupled to the processor, wherein the instructions further comprise the steps of receiving information about the measured temperature from the one or more temperature sensors, comparing the measured temperature with a second reference value, and providing a signal, including providing the signal if the difference between the measured first capacitance and the first reference value is greater than a predetermined first threshold and the difference between the measured temperature and the second reference value is greater than a predetermined second threshold.

Example 10. The device according to Example 1, the device further includes one or more optical sensors configured to image the lower side of the patient's foot when the patient stands on the base.

Example 11. A method for assessing tissue susceptibility to diabetic foot ulcer formation, the method comprising: acquiring a first capacitance value at a first location on a patient's skin; acquiring a temperature measurement value at the first location on the patient's skin; and determining that the first location on the patient's skin is susceptible to diabetic foot ulcer formation when the difference between the first capacitance value and a first reference value is greater than a first predetermined threshold and the difference between the temperature measurement value and a second reference value is greater than a second predetermined threshold.

Example 12. The method according to Example 11, wherein the first reference value is predetermined.

Example 13. The method according to Example 11, wherein the first reference value is determined by measuring the first capacitance at the first location on the patient's skin when the patient is healthy.

Example 14. The method according to Example 11, wherein the first reference value is determined by measuring the first capacitance at the first location on the patient's skin once or multiple times prior to the most recent measurement of the first capacitance.

Example 15. The method according to Example 11, wherein the first reference value is a measurement of the second capacitance of a second location of patient skin separated from the first location of patient skin.

Example 16. The method according to Example 15, wherein the second location of the patient's skin is known to be healthy.

Example 17. The method according to Example 15, wherein the second capacitor is measured almost simultaneously with the first capacitor.

Example 18. A method for assessing tissue susceptibility to diabetic foot ulcer formation, the method comprising: acquiring a first subepidermal moisture (SEM) value at a first location on a patient's skin; acquiring 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 diabetic foot ulcer formation when the difference between the first SEM value and a first reference value is greater than a first predetermined threshold and the difference between the temperature measurement value and a second reference value is greater than a second predetermined threshold.

Example 19. The method according to Example 18, wherein the first reference value is predetermined.

Example 20. The method according to Example 18, wherein the first reference value is determined by measuring the first SEM value at the first location on the patient's skin when the patient is healthy.

Example 21. The method according to Example 18, wherein the first reference value is determined by measuring the first SEM value at the first location on the patient's skin once or multiple times prior to the most recent measurement of the first SEM value.

Example 22. The method according to Example 18, wherein the first reference value is a measurement of the second SEM value of a second location of patient skin separated from the first location of patient skin.

Example 23. The method according to Example 22, wherein the second location of the patient's skin is known to be healthy.

Example 24. The method according to Example 22, wherein the second SEM value is measured almost simultaneously with the first SEM value.

Example 25. An integrated device for treating diabetic foot ulcers in patients in need, the device comprising: a plurality of sensors disposed on a flexible substrate, wherein the plurality of sensors are configured to measure subepidermal moisture (SEM) values at corresponding 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 SEM measurement, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

Example 26. The device according to Example 25 further includes an absorbent pad.

Example 27. The apparatus according to Example 25 further includes an adhesive layer.

Example 28. The apparatus according to Example 25, wherein the flexible substrate is gas-permeable but fluid-impermeable.

Example 29. An integrated device for treating diabetic foot ulcers in patients in need, the device comprising: a sensor including two electrodes disposed on a flexible substrate such that a current passing between the electrodes will pass through tissue near the patient's skin location; and an external controller electrically connected to the two electrodes.

Example 30. The integrated device according to Example 29, wherein the external controller controls the two electrodes to detect conductive contact with the patient's skin during SEM measurement, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

Although the invention has been described with reference to specific aspects, those skilled in the art will understand that various changes can be made and equivalents can be substituted for elements therein without departing from the scope of the invention. Furthermore, various modifications can be made to specific aspects or materials taught in the invention without departing from the scope of the invention. Therefore, the invention is not limited to the specific aspects disclosed, but is to include all aspects falling within the scope and spirit of the appended claims.

Claims (18)

1. An integrated device for treating diabetic foot ulcers in patients in need, the device comprising: Multiple sensors are disposed on a flexible substrate, wherein the multiple sensors are configured to measure subepidermal moisture (SEM) values at corresponding 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 controls the two electrodes to detect conductive contact with the patient's skin during SEM measurement, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase. 2. The integrated device according to claim 1 further includes an absorbent pad. 3. The integrated device according to claim 1 further includes an adhesive layer. 4. The integrated device according to claim 1, wherein the flexible substrate is gas-permeable but fluid-impermeable. 5. The integrated device of claim 1 further includes an annular pad for relieving pressure on the diabetic foot ulcer of the patient. 6. The integrated device of claim 1, wherein the external controller is periodically attached to the two electrodes during the treatment phase to apply the therapeutic stimulation. 7. The integrated device of claim 1, wherein the external controller is periodically attached to one or more of the plurality of sensors during the SEM measurement cycle to measure the SEM values. 8. The integrated device of claim 1 further includes a battery and wireless communication capability, the battery and wireless communication capability enabling the external controller to apply the therapeutic stimulation to the patient without a wired connection to the device. 9. The integrated device of claim 8, wherein the external controller further communicates with the plurality of sensors and wirelessly receives the measured SEM values. 10. The integrated device of claim 1, further comprising an integrated microcontroller configured to apply the therapeutic stimulus and measure the SEM value. 11. An integrated device for treating diabetic foot ulcers in patients in need, the device comprising: The sensor includes two electrodes disposed on a flexible substrate, such that an electric current passing between the electrodes will pass through tissue near the patient's skin location; An external controller electrically connected to the two electrodes; and The external controller controls the two electrodes to detect conductive contact with the patient's skin during SEM measurement, and the external controller also controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase. 12. The integrated device according to claim 1, wherein the therapeutic stimulus is a low-level voltage. 13. The integrated device according to claim 1, wherein the therapeutic stimulus is a low-level current. 14. The integrated device of claim 1, wherein the treatment phase comprises one or more stimulation time periods separated by one or more time intervals, each of the one or more stimulation time periods having a duration during which the therapeutic stimulus is applied, and each of the one or more time intervals having a duration during which the therapeutic stimulus is not applied. 15. The integrated device of claim 14, wherein each of the one or more time intervals is in the range of several hours. 16. The integrated device of claim 14, wherein each of the one or more time intervals is within the range of several weeks. 17. The integrated device of claim 14, wherein each of the one or more time intervals is in the range of hours or weeks. 18. The integrated apparatus of claim 14, wherein the SEM measurement period is during one or more time intervals.