WO2023245273A1

WO2023245273A1 - Wound-monitoring apparatus based on ph changes of wounds and method thereof

Info

Publication number: WO2023245273A1
Application number: PCT/CA2022/051001
Authority: WO
Inventors: Mohsen AKBARI; Brent GODAU; Armando Jardim; Shapoor SHAYEGANI
Original assignee: 4M Biotech Inc.
Priority date: 2022-06-22
Filing date: 2022-06-22
Publication date: 2023-12-28

Abstract

An apparatus for monitoring a wound. The apparatus has a sensor-containing layer and one or more sensors housed in one or more sensor regions therein the sensor-containing layer. The sensor-containing layer is for contacting the wound or exudate thereof and directing the exudate of the wound to the one or more sensors, and the one or more sensors has one or more types of pH-sensitive and pH-indicating dyes for indicating a state of the wound by changing color thereof in response to pH of the wound or the exudate thereof.

Description

WOUND-MONITORING APPARATUS BASED ON PH CHANGES OF WOUNDS

AND METHOD THEREOF

FIELD OF THE DISCLOSURE

The present disclosure relates generally to wound monitoring apparatuses and methods, and in particular to wound-monitoring apparatuses and methods using colorimetric sensors for detecting pH changes in wounds or fluids thereof for monitoring the states of the wounds.

BACKGROUND

Clinical studies have shown that the pH of acute wounds, which typically resolve within 30 days, ranges between 6.5 to 8.5 (see academic papers “Influence of pH on woundhealing: a new perspective for wound-therapy?” to Schneider et al., published in Archives of Dermatological Research 298: 413-420 (2007), and “pH profiles in human skin: influence of two in vitro test systems for drug delivery testing” to Wagner et al., published in European Journal of Pharmaceutics and Biopharmaceutics, 55:57-65 (2003)).

Chronic wounds with high rates of infection and delayed healing, typically exhibit a broader pH distribution 7.1-10 (see academic papers “The effects of pH on wound healing, bio films, and antimicrobial efficacy” to Percival et al., published in Wound Repair and d monitoring of pH and oxygen in patients after

radiation therapy” to Auerswald et al., published in Radiation Oncology, 14: 199-207 (2019)). Analysis of different regions of individual wounds revealed that the pH values near the wound center are more alkaline (pH of about 7.9), whereas the pH at the wound edges is comparable to that of the healthy skin (pH of about 6.0) (see above-referenced Auerswald et al., 2019, Radiation Oncology, 14: 199-207). It is generally assumed that a wound pH of about 8.3 and greater is infected (see above-referenced Auerswald et al., 2019, Radiation Oncology, 14: 199-207).

Colorimetric wound monitoring devices and strategies have been developed to facilitate healthcare monitoring and patient care (see academic papers “Smart Flexible Electronics-Integrated Wound Dressing for Real-Time Monitoring and On-Demand Treatment of Infected Wounds” to Pang et al., published in Advanced Science 18: https://doi.org/10.1002/advs.201902673, (2020), and “Wearable Sensors and Systems for Wound Healing-Related pH and Temperature Detection” to Tang et al., published in Micromachines 12: https://www.mdpi.eom/2072-666X/12/4/430, (2021)). However, such devices and strategies have not been widely adapted because current colorimetric wound monitoring technology is challenging to interpret and relies on the use of peripheral technology for objective indication of the presence of infections in wounds. In such technologies, the most used colorimetric dyes undergo subtle changes in color when detecting changes from pH 7.1 to 8.5 that can be described as a change in shade, tint, or tone and not a more robust and distinct change in hue, that is two visually distinct colors.

Furthermore, healing wounds and wounds in which infections are establishing, commonly produce physiological fluid exudates that mix with and interfere with the colorimetric dyes’ reaction specificities and visible color production. Another problem with such devices and technologies is that colorimetric dye molecules are small and are difficult to stably affix to substrates commonly used to prepare wound dressings while not interfering with the dyes’ chemical structures and accessibility to physiological fluids when applied to a wound.

Therefore, there is a desire for a novel wound-monitoring apparatus with reliable detection of wound states.

SUMMARY

According to one aspect of this disclosure, there is disclosed an apparatus for monitoring a wound wherein the apparatus has a wound-contacting side and a front side opposite to the wound-contacting side. The apparatus comprises a sensor-containing layer with one or more sensors disposed in one or more sensor regions in the sensor-containing layer. The sensor-containing layer is provided for contacting a wound or an exudate thereof and exposes wound exudates to the one or more sensors. The one or more sensors comprise one or more types of pH-sensitive dyes and/or pH-indicating dyes to provide a visual indication of a changing physiological state of the wound by the changing color of the dyes in response to changes in the pH of the wound or its exudate.

In some embodiments, the state of the wound is one of an uninfected acute state, a borderline state, and an infected chronic state.

In some embodiments, the one or more types of dyes may be configured to show a first color when the pH of the wound or its exudate is less than about 7.5 thereby indicating an uninfected acute state of the wound, a second color when the pH of the wound or its exudate is between 7.5 and 8.3 thereby indicating a borderline state of the wound, and a third color when the pH of the wound or its exudate is greater than 8.3 thereby indicating a chronic infected state of the wound.

In some embodiments, the first color is a substantially orange or tan color, the second color is a substantially green or brown color, and the third color is a substantially blue or green color.

In some embodiments, the color comprises a hue and/or an intensity thereof and said changing color comprises changing the hue and/or intensity thereof.

In some embodiments, the pH-sensitive dyes may be a dye compound containing a phthalein moiety for example, one or more of naphtholphthalein, thymol blue, phenolphthalein, bromothymol blue, cresol red, and/or the like.

In some embodiments, the one or more sensors further comprise a stationary-phase component for immobilizing the one or more types of dyes in the sensor regions.

In some embodiments, the stationary-phase component comprises resin.

In some embodiments, the resin comprises at least one of polystyrene, agarose, Sephadex, Sepharose, and silica.

In some embodiments, the stationary-phase component is in the form of one or more sheets.

In some embodiments, the stationary-phase component is in the form of particles. In some embodiments, the resin particles are in a range from about 20 mesh to about

400 mesh.

In some embodiments, the one or more types of dyes are loaded onto the stationary- phase particles in concentrations ranging from about 10 pg to about 10,000 pg of dye per gram of the stationary-phase component.

In some embodiments, the one or more types of dyes are loaded onto the stationary- phase particles through intermolecular interactions.

In some embodiments, the intermolecular interactions comprise hydrogen bonding, pi- pi interactions, ion-dipole interactions, and/or ion-induced dipole interactions.

In some embodiments, at least one of the sensor-containing layer and the one or more sensor regions comprise a moisture-balancing material and/or a moisture-absorbent material.

In some embodiments, the moisture-balancing material comprises one or more of a crosslinked polymer, a hydrogel, and a hydrocolloid.

In some embodiments, the moisture-absorbent material comprises one or more of a polyurethane, a non-woven fiber, a mesh fiber, a gauze, a crosslinked polymer, a hydrogel, and a hydrocolloid.

In some embodiments, the hydrogel comprises one or more of alginate, gelatin, chitosan, polyethylene glycol, poly-methyl methacrylate, poly lactic acid, polyacrylamide, and gelatin methacrylate.

In some embodiments, the sensor-containing layer is flexible. In some embodiments, the sensor-containing layer is rigid with a predefined shape for adapting to the wound.

In some embodiments, the sensor-containing layer is customizable to conform to a wound. In some embodiments, the sensor-containing layer may be transparent or semitransparent.

In some embodiments, the sensor-containing layer comprises a hydrophilic polymer.

In some embodiments, the sensor-containing layer comprises a scrim.

In some embodiments, the sensor-containing layer comprises one or more sensor backings on the wound-contacting side of the one or more sensors at locations corresponding thereto.

In some embodiments, the one or more sensor backings are opaque or non-transparent.

In some embodiments, each of the one or more sensor backings has an area greater than that of the corresponding one of the one or more sensors. In some embodiments, the one or more sensor backings comprise one or more of cellulose, hydroxyapatite, resin, psyllium, clouding agent, pigment, and opaque fibrous material.

In some embodiments, the apparatus further comprises, from the wound-contacting side to the front side opposite to the wound-contacting side, a wound-contacting layer coupled to the sensor-containing layer on the wound-contacting side thereof; and a backing liner coupled to the sensor-containing layer on the front side thereof.

In some embodiments, the wound-contacting layer, the sensor-containing layer, and the backing liner are coupled together to form a single sheet.

In some embodiments, the wound-contacting layer, the sensor-containing layer, and the backing liner are coupled together by adhesive.

In some embodiments, the wound-contacting layer is for covering a wound and allowing fluid, ions, and/or gas of the wound exudate to exude therethrough towards the one or more sensors.

In some embodiments, the wound-contacting layer comprises a porous membrane.

In some embodiments, the porous membrane comprises at least one of silicone, polyurethane, nylon, polyethylene, and polyacrylamide.

In some embodiments, the sensor-containing layer comprises the one or more sensor regions adjacent the backing liner.

In some embodiments, the backing liner comprises one or more transparent or semitransparent zones at least at locations corresponding to the one or more sensor regions.

In some embodiments, the backing liner comprises at least one of polyethylene, silicone, and cellulose acetate.

In some embodiments, the apparatus further comprises a release liner removably coupled to the wound-contacting layer on the wound-contacting side thereof. In some embodiments, the release liner comprises at least one of polyethylene, silicone, and cellulose acetate.

In some embodiments, the apparatus further comprises an adhesive border for creating an island dressing.

In some embodiments, the adhesive border comprises an absorbent material for handling excess moisture.

In some embodiments, the one or more sensors comprise two or more sets of sensors comprising two or more types of pH-sensitive and pH-indicating dyes.

In some embodiments, each of the two or more types of dyes is responsible to the pH of the wound or the exudate thereof with a corresponding set of intensity levels and/or a corresponding set of hues.

In some embodiments, the two or more types of dyes have different color-changing curves in response to the pH of the wound or the exudate thereof.

In some embodiments, the two or more types of dyes are configured for showing light colors for indicating the acute state, dark colors for indicating the chronic state, and a mixture of the light and dark colors for indicating the borderline state.

In some embodiments, the one or more sensors are configured in patterns of circles, squares, rectangles, triangles, diamonds, strips, checkers, and/or dots.

In some embodiments, the apparatus is fabricated using a liquid-deposition method, a molding method, a cast-extrusion method, and/or roll-to-roll processing. According to one aspect of this disclosure, there is disclosed a method for monitoring a wound, wherein the method comprises directing an exudate of the wound to one or more sensor regions; and using one or more types of pH-sensitive and pH-indicating dyes in the one or more sensor regions to act with the exudate of the wound to change color thereof in response to pH of the wound or the exudate thereof for indicating a state of the wound.

In some embodiments, the method further comprises using a stationary-phase component for immobilizing the one or more types of dyes in the sensor regions.

According to one aspect of this disclosure, there is disclosed a method for fabricating an apparatus for monitoring a wound wherein the method comprises depositing a noncrosslinked polymer into a mold for creating a moisture-balancing and/or a moistureabsorbent component of a sensor-containing layer of the apparatus, depositing from a first side of the body in the mold, an opaque material into the non-crosslinked polymer at one or more sensor regions for forming one or more sensor backings therein, depositing from the first side of the body in the mold, stationary-phase particles affixed with one or more types of pH-sensitive and pH-indicating dyes into the one or more sensor regions to form one or more sensors on top of the one or more opaque sensor backings; and crosslinking the polymer using a crosslinking agent.

In some embodiments, the fabrication method further comprises removing the mold, coupling a backing layer to the first side of the sensor-containing layer, and coupling a woundcontacting layer to a second side of the sensor-containing layer opposite to the first side. BRIEF DESCRIPTION OF THE DRAWINGS

These and other features of the disclosure will become more apparent in the following detailed description in which reference is made to the appended drawings, wherein:

FIG. 1 is a plain view of a wound-monitoring apparatus according to some embodiments of this disclosure, showing the outward facing, front side thereof, wherein the wound-monitoring apparatus comprises a body and one or more sensors coupled to one or more sensor regions of the body;

FIG. 2 is a cross-sectional view of the wound-monitoring apparatus shown in FIG. 1 along the cross-section line A-A;

FIG. 3 is a plan view of a portion of the wound-monitoring apparatus shown in FIG. 1 showing a sensor thereof;

FIG. 4 shows an exemplary sensor-color diagram of the wound-monitoring apparatus shown in FIG. 1;

FIG. 5 is an exemplary sensor-color diagram showing the infection-status indications of the wound-monitoring apparatus shown in FIG. 1 and how the infection-status indications represent the associated pH ranges of acute and chronic wounds;

FIG. 6 is a plan view of a wound-monitoring apparatus in the form of an island dressing, according to some embodiments of this disclosure;

FIG. 7 is a cross-sectional view of the wound-monitoring apparatus shown in FIG. 6 along the cross-section line B-B; FIGs. 8A to 8E show some exemplary patterns of the one or more sensor regions of the wound-monitoring apparatus shown in FIG. 1 or FIG. 6;

FIG. 9 is an exemplary sensor-color diagram showing the infection-status indications of the wound-monitoring apparatus shown in FIG. 1 or FIG. 6 having two groups of sensors with each sensor group comprising one or more sensors showing a specific color set (such as a specific set of color hues and/or intensity levels) when changing colors in response to the pH of the wound or the exudate thereof, according to some embodiments of this disclosure;

FIGs. 10A and 10B show an exemplary sensor-color diagram showing the infectionstatus indications of the wound-monitoring apparatus illustrated in FIGs. 1, 6, 9 having two groups of sensors with different color-changing curves, in response to the pH of the wound or the exudate thereof, according to some embodiments of this disclosure;

FIGs. 11A to 11C show the wound-monitoring apparatus shown in FIG. 1 or FIG. 6 having two groups of sensors formed in a predefined strip pattern, according to some embodiments of this disclosure;

FIGs. 12A to 12C show the wound-monitoring apparatus shown in FIG. 1 or FIG. 6 having two groups of sensors formed in a predefined checker pattern, according to some embodiments of this disclosure; and

FIGs. 13A to 13C show a process of fabricating the wound-monitoring apparatus shown in FIG. 1 or FIG. 6 using a sensor deposition methodology.

DETAILED DESCRIPTION

Embodiments of the present disclosure herein relate to apparatuses and methods of monitoring the pH of wounds and/or wound exudate with color-changing pH sensors for indicating the presence of infection in wounds.

The wound described in this disclosure refers to a breached or compromised skin surface on a human or animal. A wound described herein may refer to tom, cut, punctured, burned, or sore on animal or human skin. In some embodiments, a wound may also refer to any part of the body that can be treated by a dressing and/or a damaged area of tissue that exposes sub-epidermal layers of the skin or produces wound exudate. Examples include, but are not limited to, bums, punctures, lacerations, traumatic wounds, ulcers, sores, radiation wounds, tears, surgical wounds, dehisced wounds, incisional wounds, acute wounds, subacute wounds, chronic wounds, diabetic ulcers, decubitus ulcers, venous ulcers, combat wounds, and more.

The pH of wounds and/or wound exudate may change in accordance with the conditions of the wounds. In particular, the pH of wounds may be categorized in three ranges: acute, borderline, and chronic, and any reference of non-infected, borderline, or infected wounds herein refers to the ranges of pH associated with wounds that are acute, borderline, or chronic, respectively. Acute wounds are generally viewed as being healthy and in a prohealing state, the chronic condition is correlated with the presence of infection in the wound, and the borderline condition is a transitional condition between the acute condition and the chronic condition. For example, in some embodiments, the pH of non-infected acute wounds ranges from pH 6.5 to pH 8.3 and the pH of infected chronic wounds range from pH of 7.5 to pH 10. The overlapping region between acute and chronic (for example, from pH 7.5 to pH 8.3) is the borderline infected state (or simply the borderline state; that is, infection may be borderline).

The apparatuses disclosed herein relate to a wound dressing with incorporated colorchanging pH sensors that are continuously responsive to the pH of wounds and/or wound exudate. The wound dressing may include a body component for covering the wound and one or more sensor components configured to change color, such as to change the hue and/or intensity of the color, in accordance with changes of the pH of the wound or wound exudate. The body is configured to allow direct exposure of exudate to the sensor or to allow the transport of fluid, ions, and/or gas of exudate from the wound environment to the sensor. The colors (such as the hue and/or intensity thereof) of the one or more sensors are configured to continuously monitor wounds and robustly indicate the transition from the non-infected or acute state to the borderline infected state to an infected state and, alternatively, the transition from an infected, chronic state to the borderline state to the non-infected, acute state.

Turning now to FIGs. 1 and 2, a wound-monitoring apparatus (also denoted a wound dressing or simply a dressing) is shown and is generally identified using reference numeral 100. The wound dressing 100 may be used as a standalone dressing or in combination with other wound dressings such as primary and secondary wound dressings. For example, in some embodiments, other wound care products may be used to fill, treat, or pack the wound underneath the wound dressing 100 disclosed herein. In some other embodiments, the wound dressing 100 may be used as a wound-contact layer of another wound dressing. In yet some other embodiments, a secondary dressing may be used for, but is not limited to, adding further protection to the wound, providing a method of fixing the wound dressing 100 (and other primary dressings) to the wound, and providing added benefit to the wound-care strategy.

As shown in FIG. 1, the wound dressing 100 comprises a body 102 for covering a wound 108 and/or periwound skin 122 (collectively denoted a “wound” hereinafter for ease of description) and one or more color-changeable sensors 104 embedded in or otherwise coupled to the body 102. As will be described in more detail below, the body 102 allows the one or more color-changeable sensors 104 to contact the wound 108 and/or directs exudate produced by the wound 108 to the one or more color-changeable sensors 104, and the one or more sensors 104 may change color (such as to change the hue and/or intensity of the color) in response to the pH value of the wounds and/or wound exudate for indicating the state of the wound 108 (being the non-infected, acute state, the borderline state, or the infected, chronic state). Therefore, the wound dressing 100 may continuously monitor the wound 108 and robustly indicate the state thereof.

The body 102 (and thus the wound dressing 100) comprises a wound-contacting side 122 for contacting the wound and an outward facing, front side 124 opposite to the woundcontacting side 122 for showing the color indication (see FIG. 2), wherein FIG. 1 shows the front side 124 of the wound dressing 100. In various embodiments and use cases, the body 102 (and thus the wound dressing 100) may cover the wound 108 or may cover the wound 108 and the periwound skin 122, for example, in the cases that the wound dressing 100 is used as a sensor for a large wound (bum, combat wound, and/or the like).

In these embodiments, the body 102 is flexible and conformable to fit and form to the morphology of the wound 108, and is transparent or semi-transparent and allows visualization of the wound therethrough. The body 102 may comprise a plurality of layers formed by one or more components including but not limited to, an adhesive material, a moisture-absorbent material, a moisture-balancing material, a moisture-wicking material, a sensor-containing region or layer, an opaque or non-transparent material, a scrim, a wound-contacting porous membrane, a backing liner, a release liner, and/or the like.

As used herein, the term “moisture-absorbent material” means a material that comprises fibers and/or polymers that are capable of absorbing and holding moisture droplets and microdroplets into their micropores.

As used herein, the terms “moisture-balancing material” and “moisture-wicking material” refer to compositions that include hydrogels therein that are capable of holding water molecules within the microporous structures of the compositions. In such compositions, moisture droplets and microdroplets stay on and move on and along the surfaces of the fibers making up the composition.

As shown in FIG. 2, the body 102 comprises, from the wound-contacting side 122 to the front side 124, a wound-contacting layer 142, a sensor-containing layer 144, and a backing liner 146. Adhesive is used to adhere the layers 142, 144, and 146 together to create a single sheet.

The wound-contacting layer 142 comprises a suitable material, such as a porous membrane, for covering the wound 108 and allowing fluid, ions, and/or gas of the wound exudate to flow therethrough towards the sensors 104. Examples of the suitable porous membranes include silicone, polyurethane, nylon, polyethylene, polyacrylamide, and/or the like. The sensor-containing layer 144 comprises a body 152 with one or more sensor regions 154 adjacent the backing liner 146 for receiving therein the one or more sensors 104 and one or more sensor backings 156 “behind” the one or more sensor regions 154 (that is, at locations corresponding thereto between the sensor-containing regions 154 and the woundcontacting layer 142).

In these embodiments, the body 152 of the sensor-containing layer 144 comprises a suitable material such as hydrogel for conveying wound exudate to the one or more sensors 104, and a scrim, such as nylon, polyester, and/or the like, for added support to the hydrogel. Herein, hydrogel acts as both a moisture-absorbent material and a moisture-balancing material, and may comprise one or more of alginate, gelatin, chitosan, polyethylene glycol, poly-methyl methacrylate, poly lactic acid, polyacrylamide, gelatin methacrylate, and the like.

As will be described in more detail later, the sensor regions 154 also comprises a moisture-balancing and/or a moisture-absorbent material such as hydrogel and/or hydrocolloid to support the exposure of aqueous ions to the sensors.

The sensor backings 156 comprises a suitable material for conveying wound exudate to the one or more sensors 104. In these embodiments, the sensor backings 156 may be opaque or non-transparent and may comprise one or more of cellulose, hydroxyapatite, resin, psyllium, clouding agent, pigment, opaque fibrous material, and the like.

The backing liner 146 is made of a suitable material (such as a water-resistant material) for protecting the layers thereunder, and comprises transparent or semi-transparent zones at least at locations corresponding to the sensor regions 154 to allow the color of the sensor be visible to a user. Examples of the backing liner 146 may comprise polyethylene, silicone, cellulose acetate, and the like.

Although not shown, the wound dressing 100 in some embodiments may also comprise a release liner on the wound-contacting side 122 of the wound-contacting layer 142 for protecting the wound-contacting side of the wound dressing 100 during transportation and storage, which may be removed before application to the wound 108. Examples of suitable release liners include polyethylene, silicone, cellulose acetate, and the like.

FIG. 3 is a plan view of a portion 110 of the wound dressing 100 (see FIG. 1) showing a sensor 104 thereof, wherein the backing liner 146 in these embodiments is transparent and is not illustrated in FIG. 3. In this example, the body 152 of the sensor-containing layer 144 comprises a transparent hydrophilic polymer such as a transparent hydrogel, with a sensor region 154 and an opaque backing 156 behind the sensor region 154. The opaque backing 156 may have an area greater than that of the sensor region 154 for preventing the color of the wound or skin underneath the wound dressing 100 from interfering the color of the sensor 104, and creating a border around the sensor region 154 to visually highlight the sensor color and location.

In these embodiments, the sensor region 154 comprises one or more components for forming the sensor 104. The one or more components of the sensor region 154 may comprise, but are not limited to, one or more types of pH-sensitive, pH-indicating, colorimetric dyes for indicating the uninfected, borderline, and infected wound states and a stationary-phase component (in the form of stationary-phase particles in these embodiments) for immobilizing the pH-indicating dyes in aqueous environments to allow the pH-indicating dyes to stably affix to the sensor regions 154 of the body 102. The stationary-phase particles and the pH- indicating colorimetric dyes fixed thereon may be mixed with hydrogel which supports the exposure of aqueous ions to the colorimetric dyes.

The stationary-phase particles of the sensor 104 may comprise, but are not limited to, resin. The resin may comprise polystyrene, agarose, Sephadex, Sepharose, silica, and/or the like, and may be in the form of particles with the size in the range, for example, from about 20 mesh to about 400 mesh. Other ranges of the stationary-phase particles of the sensor 104 may also be readily available.

The pH-sensitive dyes may be a dye compound containing a phthalein moiety including naphtholphthalein, thymol blue, phenolphthalein, bromothymol blue, cresol red, and/or the like. In some embodiments, the pH-sensitive dyes are coated onto the stationary- phase particles in concentrations ranging from about 10 pg to about 10,000 pg of dye per gram of stationary-phase particles to optimize the color intensity of the sensor 104 as a function of pH at which the color change is visible. In some embodiments, the pH-sensitive dyes are fixed on the stationary-phase particles through intermolecular interactions including hydrogen bonding, pi-pi interactions, ion-dipole, ion-induced dipole interactions, and/or the like. These intermolecular means of fixation on the stationary-phase particles are employed to avoid impact on the color-changing properties of the dyes when fixing, thereby enabling the interaction of the pH-indicating dyes with ions in surrounding aqueous solution (e.g., hydrogel).

As described above, the sensors 104 are configured to indicate one or more of the noninfected, borderline, or infected states by using colors that have a high contrast to that of the wound 108 which is facilitated by an opaque or non-transparent background 156 to enable easy visualization of the sensor color. In some embodiments, the sensors 104 represent the non-infected status when first applied to the wound 108 and represent the actual status of the wound after it has equilibrated to the pH of the wound’s surface or the exudate. The sensor 104 is configured to represent a different hue when comparing the non-infected and infected states. The borderline state is a transitional color between the two unique hues that represent the non-infected and infected states.

FIG. 4 shows an exemplary sensor-color diagram 180 of the wound dressing 100 (represented using different grayscales and marked with the Hex color codes). As shown, the wound dressing 100 may show a substantially tan color (for example a with a Hex color code FFC794 or a color similar thereto) when the pH value is under 7.5 (which comprises the pH range 132 of the acute state, indicating uninfected wound), and transition to a substantially blue color (with a Hex color code 071F43 or a color similar thereto) when the pH value is above 8.3 (which comprises the pH range 136 of the chronic state, indicating infected wound). The wound dressing 100 shows a substantially green transitional color (with a Hex color code 786E4F or a color similar thereto) when the pH value is between 7.5 and 8.3 (which comprises the pH range 134 of the borderline state),

FIG. 5 is an exemplary sensor-color diagram 190 showing the infection-status indications of the wound dressing 100 and how the infection-status indications represent the associated pH ranges of acute and chronic wounds.

Thus, with the sensor regions 154 described above, the wound dressing 100 be used as a visual indicator of the non-infected, borderline, and infected status of the wound for continuously monitoring the wound states. The change in color of the sensors 104 indicates a developing infection over time if the color changes indicate moving from the uninfected state to the borderline state and then to the infected state. The change in color of the sensors 104 over time may also indicate infection subsiding if the color changes indicate moving from the infected state to the borderline state and then to the uninfected state.

A user may observe the sensor color and understand the state of the wound 108. In some embodiments, a color chart may be disclosed such that, after observing the sensor color, the user may compare the observed sensor color, shade, and/or pattern with the color chart to determine the status of the wound 108 to be uninfected, borderline, or infected.

In some embodiments, a device including a camera, such as a smartphone or tablet, may be used to image the dressing and analyze the color of the sensors 104 to determine the state of the wound 108. In some embodiments, the device may comprise an application or app for using artificial intelligence to process images of the sensors 104 and generate a more accurate status indication. For example, the application may comprise a machine vision component to guide the user to take an appropriate photo or image of the wound dressing 100 and crop the photo for easier processing, and machine learning may be used to create an algorithm for processing images of the sensors 104 to determine a wound-status output. In some embodiments, the application may be used to communicate the wound-associated images and data to another user such as a clinician, a physician, or a caretaker.

In some embodiments as shown in FIGs. 6 and 7, the wound dressing 100, or more specifically the body 102 thereof, may comprise an adhesive border 202 to create an island dressing. The adhesive border 202 may comprise an absorbent material for handling excess moisture that cannot be absorbed by the moisture-balancing body 102. Moreover, the opaque backing 156 has an area about the same as that of the sensor region 154 and thus does not create a border around the sensor region 154.

In various embodiments, the one or more sensor regions 154 (and thus the one or more sensors 104) may be configured in various patterns, such as circles, squares, rectangles, triangles, diamonds, and/or the like, for easy visualization of the pH-indicating dyes to indicate the non-infected, borderline, and infected states of the wound. FIGs. 8A to 8D show some exemplary patterns of the one or more sensor regions 154.

In some embodiments, the wound dressing 100 may comprise a plurality of sensor groups, with each sensor group comprising one or more sensors 104 showing a specific color set (such as a specific set of color hues and/or intensity levels) when changing colors in response to the pH of the wound or the exudate thereof. For example, the wound dressing 100 may comprise two sensor groups having sensors of two sets of colors wherein a first color set comprises thymol blue and the second color set comprises naphtholphthalein. That is, the first group of sensors 104- 1 may respond to the acute, borderline, and chronic states of wounds by displaying a first set of colors and the second group of sensors 104-2 may respond to the acute, borderline, and chronic states of wounds by displaying a second set of colors different from the first set of colors.

The two groups of sensors 104-1 and 104-2 may have the same color-changing curve in response to the pH of the wound or the exudate thereof such as similar to that shown in FIG. 4 (that is, the colors and/or intensity levels of the two groups of sensors 104-1 and 104- 2 may change in a similar manner with respect to the same pH values of the wounds while their colors and/or intensity levels are different); FIG. 9 shows an exemplary sensor-color diagram 240 of a wound dressing 100 having two groups of sensors, wherein the uninfected state of the wound is represented as two or more light sensor-colors, the borderline has a mix of light and dark sensor-colors, and the infected condition has all dark sensor-colors.

Alternatively, the two groups of sensors 104-1 and 104-2 may have different colorchanging curves in response to the pH of the wound or the exudate thereof. That is, the colors and/or intensity levels of the two groups of sensors 104-1 and 104-2 may change in different manners with respect to the same pH values of the wounds.

For example, as shown in the exemplary sensor-color diagram 220 of FIGs. 10A, 10B, the first group of sensors 104-1 (Dye 1) generally show a lighter color (referring to the legend of intensity 202) when the pH of the wound or wound exudate is lower than 7.5 and transition to a darker color when the wound or wound exudate is greater than 7.5. The second group of sensors 104-2 (Dye 2) generally show a lighter color (referring to the legend of intensity 202 when the pH of the wound or wound exudate is lower than 8.3 and transition to a darker color when the wound or wound exudate is greater than 8.3.

Thus, the wound dressing 100 having the two groups of sensors 104-1 and 104-2 may respond to the uninfected or acute state of wound by showing two lighter colors (may or may not be the same lighter color), respond to the borderline state of wound by showing a darker color (from the first group of sensors 104-1 or Dye 1) and a lighter color (from the second group of sensors 104-2 or Dye 2), and respond to the infected or chronic state of wound by showing two darker colors (may or may not be the same darker color). Similar to the description above, a user may directly determine the state of the wound by observing the sensor colors, using a color chart to compare with the observed sensor colors, or using a computing device with an imaging component.

In some embodiments, the plurality of sensor groups may be arranged in predefined patterns such as stripes, checkers, dots, and the like, for indicating the uninfected, borderline, and infected states of the wound. For example, FIGs. 11A to 11C show the wound dressing 100 having two groups of sensors 104-1 and 104-2 formed in a predefined strip pattern such that the wound dressing 100 (or more specifically the sensors 104- 1 and 104-2) show a light color when the wound is in the acute state (FIG. 11 A), a pattern of alternating light/dark color strips when the wound is in the borderline state (FIG. 1 IB), and a dark color when the wound is in the chronic state (FIG. 11C).

As another example, FIGs. 12A to 12C show the wound dressing 100 having two groups of sensors 104- 1 and 104-2 formed in a predefined checker pattern such that the wound dressing 100 (or more specifically the sensors 104-1 and 104-2) show a light color when the wound is in the acute state (FIG. 12A), a checker pattern of alternating light/dark colors when the wound is in the borderline state (FIG. 12B), and a dark color when the wound is in the chronic state (FIG. 12C).

As further examples, the two groups of sensors 104-1 and 104-2 may form predefined patterns similar to those shown in FIGs. 8B to 8D.

The wound dressing 100 may be fabricated using any suitable techniques such as a liquid-deposition method, a molding method, a cast-extrusion method, a roll-to-roll processing method, and/or the like. For example, in some embodiments as shown in FIGs. 13A to 13C, the wound dressing 100 may be fabricated using the liquid-deposition method and the molding method.

As shown in FIG. 13A, a polymer 302 may be deposited into a mold 304 to create the moisture balancing and/or moisture absorbent component of the sensor-containing layer 144 of the wound dressing 100. Before fully crosslinking the polymer, the opaque or nontransparent material 306 may be deposited via a nozzle 308 onto the non- or partially- crosslinked polymer 302 at one or more sensor regions 154 to suspend or dissolve therein and form the one or more sensor backings 156. As shown in FIG. 13B, the stationary-phase particles 312 (which comprise the stationary-phase component with the dyes affixed thereon) may be deposited via a nozzle 314 onto the same position of the opaque or non-transparent material 156 to suspend in the non-crosslinked polymer 302. As shown in FIG. 13C, one or more pH-sensitive sensors 104 are then formed in the one or more sensor regions 154 on top of the opaque or non-transparent backings 156 thereby creating a multi-layered sensor structure.

The mold 304 is then removed and other layers such as the wound-contacting layer 142 and the backing liner 146 are then coupled to the wound-contacting side and the front side of the sensor-containing layer 144, respectively.

In some embodiments, the mold 304 comprises polymer with a crosslinking agent configured to diffuse into the non-crosslinked polymer to create a unified structure with defined layers and regions of opaque or non-transparent material and sensor component.

In some embodiments, the wound dressing 100 may be fabricated by using castextrusion methods to create sheets or rollstock of one or more components of the body 102 of the wound dressing 100, including the moisture-absorbent material, the moisture-balancing material, the sensor containing region or layer, the opaque or non-transparent material, and/or the like. In this method, a liquid material is extruded into a sheet conveyed by roll-to-roll or belt conveyance and is cured chemically, thermally, or by light to generate rolls of each individual dressing body component. A scrim may be incorporated into the cast-extruded sheet to strengthen the sheet. The rolls are then further processed using dye-cutting and rollslitting methods to create individual dressing components in desired sizes and shapes that may be assembled into the wound dressing 100 with multiple layers and/or regions.

In some embodiments, rollstock of one or more components of the body 102 of the wound dressing 100, including the moisture-absorbent material and/or the moisture-balancing material, is dye cut to create wells for depositing one or more of the sensor-containing region or layer, the opaque or non-transparent material, and curing chemically, thermally, or by light to generate rolls of the body of the wound dressing material with defined layers and regions of opaque or non-transparent material and sensor component.

Those skilled in the art will appreciate that other embodiments are also readily available. For example, in some embodiments, the wound dressing 100 is non-adherent, meaning that it does not adhere to the wound 108 or contain any adhesive in the formulation. In these embodiments, the layers 142, 144, and 146 are stacked together and attached to the wound 108 using suitable means such as secondary dressings and/or tapes.

In above embodiments, the body 102 is flexible and conformable to fit and form to the morphology of the wound 108. Alternatively, the body 102 may be rigid with a predefined shape for adapting to the contouring surfaces of the body about the wound 108 and protecting the wound 108 from external forces. Yet alternatively, the body 102 may be customizable by a user (such as a physician, a nurse, or a patient) to adapt to the contouring surfaces of the body about the wound 108 and still maintain sufficient rigidity for protecting the wound 108 from external forces.

In above embodiments, the body 102 is transparent or semi-transparent. However, those skilled in the art appreciate that the body 102 may be opaque or non-transparent in some other embodiments.

In above embodiments, the body 152 of the sensor-containing layer 144 comprises hydrogel for directing wound exudate to the one or more sensors 104 which acts as both a moisture-absorbent material and a moisture-balancing material. In some embodiments, the body 152 of the sensor- containing layer 144 may comprise a moisture-balancing material (which may or may not include an adhesive component) such as one or more of crosslinked polymer, hydrogel, hydrocolloid, and the like. In some other embodiments, the body 152 of the sensor-containing layer 144 may comprise a moisture-absorbent material (which may or may not include an adhesive component) such as one or more of polyurethane, non-woven fiber, mesh fiber, gauze, crosslinked polymer, hydrogel, hydrocolloid, and the like.

In some embodiments, the body 152 of the sensor-containing layer 144 may comprise both a moisture-balancing material and a moisture-absorbent material. The moisturebalancing and moisture-absorbent materials may be the same material or may be different materials.

In above embodiments, the body 152 of the sensor-containing layer 144 comprises a scrim for added support to the moisture-balancing and/or material moisture-absorbent materials such as hydrogel. In some embodiments, the body 152 of the sensor-containing layer

144 may not comprise a scrim.

In some other embodiments, the sensor backings 156 may be transparent. In some embodiments, the sensor-containing layer 144 may not comprise any sensor backings 156. The stationary-phase component of the sensor 104 may be in the form of one or more sheets which, for example, may be suitable for fabrication using cast-extrusion methods.

In above embodiments, the sensor region 154 comprises the pH-sensitive dyes and the stationary-phase component. In some embodiments, the sensor region 154 may not comprise any stationary-phase component. Although embodiments have been described above with reference to the accompanying drawings, those of skill in the art will appreciate that variations and modifications may be made without departing from the scope thereof as defined by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. An apparatus for monitoring a wound, the apparatus having a wound-contacting side and a front side opposite to the wound-contacting side, and comprising: a sensor-containing layer; and one or more sensors received in one or more sensor regions the sensor-containing layer; wherein the sensor-containing layer is for contacting a wound location or the wound or an exudate thereof and directing the exudate of the wound to the one or more sensors; and wherein the one or more sensors comprise one or more types of pH-sensitive and pH- indicating dyes for indicating a state of the wound by changing a hue and/or an intensity of a color thereof in response to pH of the wound or the exudate thereof to thereby indicate that the state of the wound is one or more of an uninfected state, a borderline state, an infected chronic state, and an acute infected state,

2. The apparatus of claim 1, wherein the one or more types of dyes are configured to show a first color when the pH of the would location or the wound or the exudate thereof is smaller than about 7.5 indicating an uninfected acute state of the wound location or the wound or the exudate, a second color when the pH of the wound location or the wound or the exudate thereof is between 7.5 and 8.3 indicating a borderline state of the wound, and a third color when the pH of the wound location or the wound or the exudate thereof is greater than 8.3 indicating an infected chronic state of the wound.

3. The apparatus of claim 1 or 2, wherein the first color is a substantially tan color, the second color is a substantially green color, and the third color is a substantially blue color.

4. The apparatus of any one of claims 1 to 3, wherein the one or more types of dyes comprise a phthalein moiety.

5. The apparatus of claim 4, wherein the phthalein moiety is one or more of thymol blue, naphtholphthalein, phenolphthalein, bromothymol blue, and cresol red.

6. The apparatus of any one of claims 1 to 5, wherein the one or more sensors further comprise a stationary-phase component for immobilizing the one or more types of dyes in the sensor regions.

7. The apparatus of claim 6, wherein the stationary-phase component comprises a resin.

8. The apparatus of claim 7, wherein the resin comprises at least one of polystyrene, agarose, Sephadex, Sepharose, and silica.

9. The apparatus of claim 7 or 8, wherein the stationary-phase component is in a form of one or more sheets.

10. The apparatus of claim 7 or 8, wherein the stationary-phase component is in a form of resin particles.

11. The apparatus of claim 10, wherein the resin particles are in a range from about 20 mesh to about 400 mesh.

12. The apparatus of any one of claims 6 to 11, wherein the one or more types of dyes are loaded onto the stationary-phase particles in concentrations ranging from about 10 pg to about 10,000 pg of dye per gram of the stationary-phase component.

13. The apparatus of any one of claims 6 to 12, wherein the one or more types of dyes are loaded onto the stationary-phase particles through intermolecular interactions.

14. The apparatus of claim 13, wherein the intermolecular interactions comprise hydrogen bonding, pi-pi interactions, ion-dipole, and/or ion-induced dipole interactions.

15. The apparatus of any one of claims 1 to 14, wherein at least one of the sensor-containing layer and the one or more sensor regions comprise a moisture-balancing material and/or a moistureabsorbent material.

16. The apparatus of any one of claims I to 15, wherein the moisture-balancing material comprises one or more of crosslinked polymer, hydrogel, and hydrocolloid.

17. The apparatus of any one of claims 1 to 15, wherein the moisture-absorbent material comprises one or more of polyurethane, non-woven fiber, mesh fiber, gauze, crosslinked polymer, hydrogel, and hydrocolloid.

18. The apparatus of claim 16 or 17, wherein the hydrogel comprises one or more of alginate, gelatin, chitosan, polyethylene glycol, poly-methyl methacrylate, poly lactic acid, polyacrylamide, and gelatin methacrylate.

19. The apparatus of any one of claims 1 to 18, wherein the sensor-containing layer is flexible.

20. The apparatus of any one of claims 1 to 18, wherein the sensor-containing layer is rigid with a predefined shape for adapting to the wound.

21. The apparatus of any one of claims 1 to 18, wherein the sensor-containing layer is customizable to adapt to the wound location or the wound.

22. The apparatus of any one of claims 1 to 21, wherein the one or more sensors are opaque or nontransparent, and the sensor-containing layer is transparent or semi-transparent.

23. The apparatus of any one of claims 1 to 22, wherein the sensor-containing layer comprises a hydrophilic polymer.

24. The apparatus of any one of claims 1 to 23, wherein the sensor-containing layer comprises a scrim.

25. The apparatus of any one of claims 1 to 24, wherein the sensor-containing layer comprises one or more sensor backings on the wound-contacting side of the one or more sensors at locations corresponding thereto.

26. The apparatus of claim 25, wherein the one or more sensor backings are opaque or nontransparent.

27. The apparatus of claim 25 or 26, wherein each of the one or more sensor backings has an area greater than that of the corresponding one of the one or more sensors.

28. The apparatus of claim 25 or 27, wherein the one or more sensor backings comprise one or more of cellulose, hydroxyapatite, resin, psyllium, clouding agent, pigment, and opaque fibrous material.

29. The apparatus of any one of claims 1 to 28 further comprising, from the wound-contacting side to the front side opposite to the wound-contacting side, a wound-contacting layer coupled to the sensor-containing layer on the wound-contacting side thereof; and a backing liner coupled to the sensor-containing layer on the front side thereof.

30. The apparatus of claim 29, wherein the wound-contacting layer, the sensor-containing layer, and the backing liner are coupled together forming a single sheet.

31. The apparatus of claim 29, wherein the wound-contacting layer, the sensor-containing layer, and the backing liner are coupled together by adhesive.

32. The apparatus of any one of claims 29 to 31, wherein the wound-contacting layer is for covering the wound and allowing fluid, ions, and/or gas of the wound exudate to transport therethrough towards the one or more sensors.

33. The apparatus of any one of claims 29 to 32, wherein the wound-contacting layer comprises a porous membrane.

34. The apparatus of claim 33, wherein the porous membrane comprises at least one of silicone, polyurethane, nylon, polyethylene, and polyacrylamide.

35. The apparatus of any one of claims 29 to 34, wherein the sensor-containing layer comprises the one or more sensor regions adjacent the backing liner.

36. The apparatus of any one of claims 29 to 35, wherein the backing liner comprises one or more transparent or semi-transparent zones at least at locations corresponding to the one or more sensor regions.

37. The apparatus of any one of claims 29 to 36, wherein the backing liner comprises at least one of polyethylene, silicone, and cellulose acetate.

38. The apparatus of any one of claims 29 to 37 further comprising a release liner removably coupled to the wound-contacting layer or the sensor contacting layer on the wound-contacting side thereof.

39. The apparatus of claim 38 wherein the release liner comprises at least one of polyethylene, silicone, and cellulose acetate.

40. The apparatus of any one of claims 1 to 39 further comprising: an adhesive border for creating an island dressing.

41. The apparatus of claim 40, wherein the adhesive border comprises an absorbent material for handling excess moisture.

42. The apparatus of any one of claims 1 to 41, wherein the one or more sensors comprise two or more sets of sensors comprising two or more types of pH-sensitive and pH-indicating dyes.

43. The apparatus of claim 42, wherein each of the two or more types of dyes is responsive to the pH of the wound or the exudate thereof with a corresponding set intensity levels and/or a corresponding set of hues.

44. The apparatus of claim 42 or 43, wherein the two or more types of dyes have different colorchanging curves in response to the pH of the wound or the exudate thereof.

45. The apparatus of any one of claims 1 to 44, wherein the two or more types of dyes are configured for showing light colors for indicating the acute state, intense colors for indicating the chronic state, and a mixture of the light and intense colors for indicating the borderline state.

46. The apparatus of any one of claims 1 to 45, wherein the one or more sensors are configured in patterns of circles, squares, rectangles, triangles, diamonds, strips, checkers, and/or dots.

47. The apparatus of any one of claims 1 to 46, wherein the apparatus is fabricated using a liquiddeposition method, a molding method, a cast-extrusion method, and/or roll-to-roll processing.

48. A method for monitoring a wound, the method comprising: directing an exudate of the wound to one or more sensor regions; and using one or more types of pH-sensitive and pH-indicating dyes in the one or more sensor regions to act with the exudate of the wound to change color thereof in response to pH of the wound or the exudate thereof for indicating a state of the wound.

49. The method of claim 48, further comprising: using a stationary-phase component for immobilizing the one or more types of dyes in the sensor regions.

50. A method for fabricating an apparatus for monitoring a wound, the method comprising: depositing a non-crosslinked polymer into a mold for creating a moisture balancing and/or a moisture absorbent component of a sensor-containing layer of the apparatus; depositing, from a first side of the body in the mold, an opaque material into the noncrosslinked polymer at one or more sensor regions for forming one or more sensor backings therein; depositing, from the first side of the body in the mold, stationary-phase particles affixed with one or more types of pH-sensitive and pH-indicating dyes into the one or more sensor regions to form one or more sensors on top of the one or more opaque sensor backings; and crosslinking the polymer using a crosslinking agent.

51. The method of claim 50, further comprising: removing the mold; coupling a backing layer to the first side of the sensor-containing layer; and coupling a wound-contacting layer to a second side of the sensor-containing layer opposite to the first side.