WO2023178034A1 - Système et procédé de détection d'oxygène pour la prédiction, la détection, l'atténuation et/ou la prévention d'une lésion cutanée péristomiale - Google Patents

Système et procédé de détection d'oxygène pour la prédiction, la détection, l'atténuation et/ou la prévention d'une lésion cutanée péristomiale Download PDF

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Publication number
WO2023178034A1
WO2023178034A1 PCT/US2023/064228 US2023064228W WO2023178034A1 WO 2023178034 A1 WO2023178034 A1 WO 2023178034A1 US 2023064228 W US2023064228 W US 2023064228W WO 2023178034 A1 WO2023178034 A1 WO 2023178034A1
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WIPO (PCT)
Prior art keywords
wearable sensor
oxygen
peristomal skin
oxygen consumption
phosphorescence
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PCT/US2023/064228
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English (en)
Inventor
Olivia E. DUNNE
Alison C. GILL
Kristen GOTSIS
Tarek JABRI
Adrian P. Defante
Abram D. Janis
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Hollister Incorporated
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Publication of WO2023178034A1 publication Critical patent/WO2023178034A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14556—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases by fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4842—Monitoring progression or stage of a disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683—Means for maintaining contact with the body
    • A61B5/6832—Means for maintaining contact with the body using adhesives
    • A61B5/6833—Adhesive patches

Definitions

  • the present disclosure pertains to a film-like adhesive sensor applied as a liquid or gel for an ostomy system. More particularly, the present disclosure pertains to an adhesive film sensor for detecting skin oxygen consumption and inflammation on peristomal skin.
  • the skin is the largest organ and functions as a part of the innate immune response by initiating mechanisms to combat toxins, pathogens, and physical stressors. It is the body’s first physical defense against external pathogens.
  • the skin itself is made up of three main layers: the dermis, the epidermis, and the hypodermis.
  • the epidermis can be broken down into the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.
  • the stratum basale of the epidermis consists primarily of undifferentiated cells undergoing mitosis, and cells eventually differentiate from this layer to form the stratum spinosum.
  • the stratum spinosum produces keratin, a structural protein that plays a role in protecting epithelial cells from damage.
  • the stratum granulosum is composed of keratinocytes, which play an essential role in skin repair and re-epithelialization.
  • the stratum lucidum is a smooth, seemingly translucent layer of the epidermis located just above the stratum granulosum and below the stratum corneum. This thin layer of cells is generally found in the thick skin of the palms, soles, and digits.
  • the stratum corneum contains mature keratinocytes and functions to maintain body temperature, as well as prevent harmful water loss or absorption.
  • the acid mantle is a term used to describe the acidic property of the stratum corneum, ranging from a pH of about 4.4-6.
  • the acid mantle is part of the outermost layer of skin and, therefore, truly the first response against harmful foreign materials.
  • the lipid-rich stratum corneum can also protect against transepidermal water loss by helping the skin retain moisture. However, as this layer is thin and delicate, it may be easily damaged, by mechanical or chemical means, which can subsequently leave the skin exposed and more vulnerable to infection.
  • Certain medical procedures can create a cutaneous environment that is susceptible to mechanical and chemical injury.
  • An ostomy is a surgery that creates an opening in the abdomen, called a stoma, that enables a connection between the small or large intestines and the skin surface.
  • the stoma is created by the diversion of the intestine to the lower quartile of the abdomen and functions as an anus for the disposal of bodily waste products.
  • patients After the procedure, patients generally live with an ostomy pouch that is attached to the area around the stoma through adhesion to the skin and collects waste products.
  • PSC Peristomal skin complications
  • a system and method for detecting oxygen levels of the skin for the prediction, mitigation, detection, and prevention of peristomal skin injury and pressure injury is provided according to various embodiments.
  • a system for predicting, detecting, mitigating, and/or preventing peristomal skin injury may include a wearable sensor film adhesive.
  • the wearable sensor may include phosphorescent metal loporphyrin molecules that are excited by pulses of light based on oxygen consumption.
  • the system may also include a light sensor.
  • the light sensor may detect phosphorescence from the wearable sensor.
  • the system may further include a computing unit. The computing unit may determine a peristomal skin injury based on the detected phosphorescence.
  • the wearable sensor may be mounted to peristomal skin.
  • the wearable sensor adhesive film can be applied as a liquid or gel that may be affixed to the peristomal skin.
  • the computing unit may detect the peristomal skin injury by measuring an oxygen consumption rate on the wearable sensor based on the detected phosphorescence.
  • the system may further include a light unit.
  • the light unit may output light pulses to excite the phosphorescent metalloporphyrin molecules.
  • the image sensor may be attached to at least part of an area of the wearable sensor.
  • the image sensor may include a handheld device.
  • the wearable sensor may include an ethanol-based adhesive film applied as a liquid or gel.
  • the ethanol-based adhesive film can be a gel or liquid bandage.
  • the ethanol-based gel or liquid adhesive may include an esterified oxyphor solution and coumarin.
  • the ethanol -based gel or liquid adhesive may be painted onto an area of peristomal skin.
  • the wearable sensor may include an alginate hydrogel.
  • the alginate hydrogel may include CaS0 4
  • a method for detecting peristomal skin injury may be applied to a computing device or unit and may include outputting light pulses, through a light output device, onto a wearable sensor mounted on peristomal skin.
  • the wearable sensor may include phosphorescent metalloporphyrin molecules that are excited by pulses of light based on oxygen consumption.
  • the computing device may also obtain phosphorescence intensity levels of the phosphorescent metalloporphyrin molecules excited by the pulses of light.
  • the computing device may further determine the development of or healing of a peristomal skin injury based on the phosphorescence intensity levels.
  • the computing device may further measure an oxygen consumption rate on the wearable sensor based on the phosphorescence intensity levels.
  • the computing device may also determine the status of a peristomal skin injury based on the oxygen consumption rate.
  • the wearable sensor may include a film-like adhesive applied as a liquid .
  • the consumption rate may include a constant rate during a measurement period and a rate of diffusion out of the fdm-like adhesive can be constant and directly related to the oxygen consumption rate under the fdm-like adhesive.
  • the fdm-like adhesive can be painted on the peristomal skin.
  • the fdm-like adhesive can be an oxygen sensing fdm.
  • the computing device may also obtain a phosphorescence image of the wearable sensor.
  • a computing device for detecting peristomal skin injury.
  • the computing device may include one or more processors, a non- transitory computer-readable memory storing instructions executable by the one or more processors.
  • the one or more processors may be configured to obtain phosphorescence intensity levels of a wearable sensor mounted on peristomal skin.
  • the wearable sensor may include phosphorescent metalloporphyrin molecules.
  • the one or more processors may also be configured to measure an oxygen consumption rate on the wearable sensor based on the phosphorescence intensity levels.
  • the one or more processors may further be configured to determine a peristomal skin injury based on the oxygen consumption rate.
  • the wearable sensor may include a film-like adhesive applied as a liquid or gel.
  • the consumption rate may include a constant rate during a measurement period and a rate of diffusion out of the film-like adhesive can be constant and directly related to the oxygen consumption rate under the film-like adhesive.
  • FIG. 1 is a front view of a wearable sensor attached to a user, according to an embodiment.
  • FIG. 2 is a diagrammatical section view of a wearable sensor attached to a user’s peristomal skin, according to an embodiment.
  • FIG. 3 is a front view of a system for detecting a peristomal skin injury, according to an embodiment.
  • FIG. 4A is a front view of a user’s abdomen with a stoma and peristomal skin inflammation.
  • FIG. 4B is a front view of the user’s abdomen of FIG. 4A with a wearable sensor surrounding the stoma in accordance with embodiments presented herein.
  • FIG. 4C is an oxygen-sensing image of the wearable sensor of FIG. 4B.
  • FIG. 5 is a graphical illustration of a prior art Jablonski diagram of the electronic states of a porphyrin interacting with an oxygen molecule.
  • FIG. 6 is an illustration of a prior art Oxyphor R4 (red) and Oxyphor G4 (green).
  • FIG. 7A is a graphical illustrating the curved results of oxygen consumption rate measurements.
  • FIG. 7B is a graphical illustrating the linear results of oxygen consumption rate measurements.
  • FIG. 8 A is a graph illustrating data produced for phosphorescence of oxyphor R4.
  • FIG. 8B is a graph illustrating data produced for phosphorescence of time averaged oxyphor R4.
  • FIG. 8C is a graph illustrating data produced for phosphorescence over time.
  • FIG. 9A is a graph illustrating data produced for phosphorescence of oxyphor R4.
  • FIG. 9B is a graph illustrating data produced for phosphorescence of time averaged oxyphor R4.
  • FIG. 10A is a graph illustrating data produced for phosphorescence of oxyphor R4.
  • FIG. 10B is a graph illustrating data produced for fluorescence as a function of oxygen consumption rate.
  • FTG. 11 is a flow diagram illustrating a method for detecting peristomal skin injury, according to another embodiment.
  • FIG. 12 is a schematic illustration of a computing environment, according to an embodiment.
  • the present disclosure provides a wearable film system applied as a liquid or gel for detecting skin oxygen consumption and inflammation on peristomal skin.
  • the wearable film can be part of an oxygen sensing film system that can include a wearable sensor that can allow monitoring of critical changes in oxygen consumption in the peristomal skin, as a proxy for skin damage caused by the stoma and ostomy bags.
  • the wearable sensor can be a standard patient point- of-care diagnostic or indicator tool.
  • the wearable sensor can allow researchers to investigate the effect of physical and chemical irritants on the skin as well as explore the oxygenation state of the occluded peristomal skin in general.
  • the oxygen sensing system can include a computing unit that can provide alerts regarding impending or resolving peristomal skin conditions for user intervention.
  • the peristomal skin injury can include inflamation, irritation and redness, fungal or bacterial infections, allergic reactions to an adhesive used to hold the ostomy pouch in place, pressure ulcers caused by the weight of the pouch or tight clothing, trauma from accidental removal or dislodgement of the pouch, fissures or tears in the skin caused by straining during bowel movements. Pressure ulcers can include bed sores.
  • Skin injury and associated inflammation can have a significant effect on the tissue microenvironment, including increased oxygen consumption by highly metabolically active resident cells and recruited inflammatory cells. Normal wound- healing consists of four main stages — hemostasis, inflammation, proliferation, and remodeling — and sufficient oxygenation is a key component of healing. As a critical aspect of cell metabolism, oxygen prevents wounds from infection, induces angiogenesis, increases keratinocyte differentiation, migration, and re-epithelialization, enhances fibroblast proliferation and collagen synthesis, and promotes wound contraction.
  • FIG. 1 illustrates a wearable sensor 14 mounted on a user.
  • the wearable sensor 14 can be applied to peristomal skin around a stoma 12.
  • the wearable sensor 14 can be used for transcutaneous oxygen monitoring based on phosphorescence emission of a metalloporphyrin embedded in a breathable oxygen-sensing film.
  • the wearable sensor 14 can be a liquid or gel film that can be painted on the peristomal skin.
  • the wearable sensor 14 can be a bandage, dressing, coating or barrier that can attach to a user’s peristomal skin.
  • oxygenation monitoring can include the use of the fluorescence emissions of phosphors embedded in a thin, oxygen-permeable liquid or gel film, to measure tissue oxygenation at the skin surface.
  • the phosphors can undergo quenching in the presence of oxygen, so tracking the lifetime and intensity of phosphorescence can correlate directly to the progression of skin inflammation over time.
  • the feasibility of such a device can be proven in preliminary in vivo testing models with consistently reproducible results between devices and calibrations.
  • the device can include machine learning models and remote monitoring.
  • FIG. 2 illustrates a diagrammatic section view of a wearable sensor 114.
  • the wearable sensor 114 can be attached to a user’s skin 112 on one side and be exposed to atmospheric oxygen 110 on the other.
  • the wearable sensor 114 can be a liquid bandage or an oxygen-sensing bandage that can include phosphorescent metalloporphyrin molecules that can be excited by pulses of light.
  • the liquid bandage 114 can transcutaneously monitor oxygen based on inflamed tissue 116 consuming oxygen more rapidly than healthy tissue.
  • FIG. 3 illustrates a system 200 for detecting a peristomal skin injury.
  • the system 200 can include a liquid or gel bandage or fdm 214, a light sensor unit 216, a sensor interface 218, and a computing unit 220.
  • the liquid bandage or fdm 214 can include phosphorescent metalloporphyrin molecules that can be excited by pulses of light based on oxygen consumption.
  • the light sensor unit 216 can include a phosphorimeter, a camera or other photosensitive sensors capable of detecting phosphorescence.
  • the light sensor unit 216 can also include a light unit such as a light out device, LED, flashlamp, or laser that can output light pulses.
  • the light sensor unit 216 can be mounted to cover an area of the liquid bandage 214.
  • the light sensor unit 216 can output light pulses and measure the phosphorescent output of the covered area of the liquid bandage or fdm 214.
  • the light sensor unit 216 can be placed along or adjacent an area where inflammation is most likely to occur.
  • the light sensor unit 216 can be placed at an area close to the stoma (an inner ring of the liquid bandage 214), where irritation and inflammation can occur due to its proximity to stoma output.
  • the light sensor unit 216 can be placed at an area below the inner ring of the oxygen sensing liquid, gel or fdm 214, near a user’s hip (where stoma output could descend due to gravity).
  • the light sensor unit 216 can cover the entire oxygen sensing liquid or gel bandage 214 to measure the phosphorescent output of the entire liquid bandage 214 (FIG. 4C).
  • the senor 216 can include small battery-powered systems with oxyphor-based sensor heads.
  • the sensor interface 218 can comprise connecting wires that can electronically connect the sensor 216 and computing unit 220 to acquire data from the light sensor unit 216.
  • the computing unit 220 can analyze the acquired data to determine oxygen consumption (see FIG. 15).
  • FIG. 4A shows a user’s abdomen with a stoma 312 and inflamated peristomal skin 322.
  • FIG. 4B shows the user’s abdomen of FIG. 4A with the stoma 312 and a liquid bandage 314 attached over the peristomal skin.
  • FIG. 4C shows a captured image 324 of a liquid bandage 326 with a detected oxygen consumption area 328.
  • the captured image 324 can be captured by a sensor (such as sensor 116) being placed in front of the liquid bandage 314.
  • the sensor can be a handheld device such as a mobile phone having a camera or other image capture device/sensor.
  • a patient, user or clinician can apply the liquid bandage when an ostomy bag is changed to detect inflammation while the ostomy bag is worn.
  • the wearable sensor can be incorporated into a barrier adhesive and the barrier can have openings and mechanical mechanisms to expose the liquid bandage for measuring phosphorescence. This method could allow for more frequent measurements of the oxygen consumption rate.
  • a computing unit could also be incorporated therein to push automatic alerts to medical professionals allowing rapid intervention if a peristomal skin condition is developing.
  • the computing unit can provide haptic feedback, sound, and light alerts.
  • the wearable sensor 14, 114, 214 can include an ethanol-based gel or liquid bandage (such as NEW-SKIN®), embedded with phosphorescent molecules.
  • the phosphorescent molecules can include Oxyphor R2 and Coumarin 500 that may be used as a red, oxygen-sensing dye and a green reference dye, respectively.
  • the excitation and emission wavelengths of the two dyes in the liquid bandage can icnclude:
  • a mechanism of porphyrin phosphorescence can include Oxyphor R2.
  • Oxyphor R2 may be categorized as a porphyrin molecule, which is a heterocyclic organic compound that consists of four modified pyrrole subunits, which are connected via methine bridges at the a-carbon atom.
  • Metal complexes comprising porphyrins and/or metalloporphyrins occur naturally and these molecules may be found throughout the human body. For example, heme is an iron-containing porphyrin complex found in hemoglobin.
  • Porphyrins may demonstrate a certain luminescent emission, phosphorescence, which is light emission similar to fluorescence, but on a longer timescale that can continue after initial excitation. After being excited by exposure to a photon, most porphyrins undergo internal conversion to an initial singlet state over a picosecond timescale. Then, the porphyrin may quickly change the configuration to form a metastable triplet state. Triplet state formation is typically very efficient in porphyrins, and certain irregular metalloporphyrins have electronic spectra that are significantly affected by their central atoms. Several Pt(II) and Pd(II) complexes display hypsochromic spectra, which means that triplet state formation enables a particularly strong emission of phosphorescence.
  • Molecular triplets have a tendency to interact with other molecular triplets.
  • One of the most prevalent molecular triplets in nature is oxygen.
  • the excited triplet states of Pt and Pd porphyrins have been shown to be effectively quenched by molecular (triplet) oxygen both in solid- state oxygen-permeable materials and in solutions.
  • Pd(II) porphyrins have lifetimes on the order of approximately 500-1000 ps, which are ten times longer than the half-lives of Pt(II) porphyrins and better-suited to measuring low oxygen levels.
  • porphyrin triplets interact with oxygen triplets, they transfer energy to the oxygen molecules before the porphyrins phosphoresce.
  • FIG. 5 illustrates a prior art Jablonski diagram of the electronic states of a porphyrin interacting with an oxygen molecule.
  • Oxyphor R4 in particular, is a metalloporphyrin derived from phosphorescent Pd- meso-tetra-(3,5-dicarboxyphenyl)-porphyrin (PdP). This porphyrin is highly soluble in aqueous environments and is known to not permeate biological membranes.
  • FIG. 6 illustrates structures of a prior art Oxyphor R4 and Oxyphor G4.
  • the liquid bandage can include oxyphor that can be esterified in order to enhance the compatibility of the dye with the ethanol-based liquid bandage matrix.
  • Esterified Oxyphor R2 may then be mixed with Coumarin and NEW-SK1N® liquid bandage in order to formulate the liquid bandage. This mixture can be painted onto a small area of skin and, within several minutes of air-drying, the liquid should harden into a thin film.
  • the oxygen consumption rate under an oxygen sensing film applied as a liquid or gel bandage can be used as a proxy for skin inflammation. It can be assumed that this rate of consumption is constant during the measurement period, and the rate of diffusion out of the liquid bandage can be constant and directly related to the oxygen consumption rate under the bandage. In addition, there is constant O 2 content in the air in contact with the upper surface of the sensing fdm. Given a constant concentration on the exposed side and a constant diffusion rate on the other, the system can eventually reach a state of equilibrium in which the oxygen content of the bandage is constant and can be directly related to the oxygen consumption rate under it. Consequently, the equilibrium oxygen content in the liquid bandage after application on the skin can be used as a proxy for skin inflammation.
  • metalloporphyrin can demonstrate measurable changes in phosphorescence emission intensity with changing oxygen content inside the bandage. Therefore, the equilibrium phosphorescence emission can be used as a proxy for skin inflammation.
  • tegaderm can be used as a top layer on the liquid bandage to control oxygen levels.
  • the liquid bandage can be exposed to atmospheric oxygen since the rate of oxygen consumption in the skin can be related to the partial pressure of oxygen in the bandage and thus to the phosphorescence intensity at equilibrium.
  • the model can be validated by directly relating the phosphorescence intensity to known values of oxygen consumption rate, show a change in phosphorescence with inflammation, and test new formulations of the liquid bandage with different porphyrins.
  • a model of oxygen consumption can be used. Solutions of cells such as yeast in different concentrations can be used. In order to relate the concentration of cells to the average rate of oxygen consumption, an oxygen meter can be used.
  • the liquid bandage can be prepared using Oxyphor G4, Oxyphor R4, and Oxyphore without the control green dye (Coumarin)
  • a time until the equilibration of oxygen flux between the atmosphere, the bandage, and the oxygen consuming medium underneath can be determined.
  • a thin layer of liquid bandage can be solidified on a glass slide then transferred on top of the wells containing the solutions of cells with different concentrations. Measurements of the red and green emission intensities can be taken thereafter on the order of every two minutes for at least 20 minutes.
  • the partial pressure of oxygen in the bandage can be calculated using the emission intensity given equation (1). This result can allow a validation of the relation between the difference in pO 2 at equilibrium and in the air and the known oxygen consumption rates. Consequently, a clear relationship between the intensity of emissions and the oxygen consumption rate can be acquired, which is a direct measure of inflammation. This calibration can also be done for new liquid bandage formulations, including Oxyphor G4, which might result in greater sensitivity.
  • near-infrared (NIR) imaging of the incorporated fluorophores can be used to extract meaningful information from the liquid bandage.
  • Thyristor(R) Speedlight flash units with the proper bandpass fdters can be used to excite the dyes and a NIR complementary metal-oxide-semiconductor (CMOS) camera with a macro lens and a digital delay/pulse generator to capture the resultant fluorescence.
  • CMOS complementary metal-oxide-semiconductor
  • IVIS in vivo imaging system
  • Another potential imaging system can include an 3i Lattice Lightsheet Microscope with Bessel Beam Illumination. This microscope can include a CMOS NIR camera.
  • a solidified liquid bandage of thickness containing dyes can be deposited on the skin which consumes oxygen with a constant (negative) rate Ren. skin.
  • the surface of the bandage can be in contact with the air which has a constant oxygen content at a partial pressure pCh(air).
  • An amount of oxygen inside the bandage given diffusion from the air into it and out of it to the skin can be calculated.
  • the change in oxygen content can be described by the following mass transport equation:
  • R 02 is the bulk reaction rate and is the flux of oxygene described by:
  • D 02 is the diffusivity of oxygen in the material considered and v is the bulk velocity.
  • BC2 flux out of the bandage equal to flux into the skin at the interface
  • BC3 assume that the superficial skin layer of thickness d s is supplied by the diffusion of oxygen from the atmosphere, and beyond this depth the tissue oxygen is supplied by circulation.
  • the oxygen content inside the bandage at steady-state can be directly related to the oxygen consumption rate under it.
  • the oxygen content inside the bandage can also be related to the intensity of Oxyphore R4 emission using the Stern- Volmer equation, the intensity of emission can be a proxy for skin level inflammation where a greater intensity corresponds to less oxygen in the bandage, so a higher oxygen consumption rate in the skin can be representative of a higher level of inflammation.
  • a yeast model can be very similar to the skin model but with slight differences.
  • the yeast solution can be placed in a well with depth d w and can consume oxygen at a rate
  • 3 ⁇ 4 of the well can be filled with the yeast solution (0.3mL) while the top 1 ⁇ 4 contains air which it can be assumed does not have a bulk velocity either.
  • BC2 flux out of the bandage equal to flux into air 2 at the interface
  • BC3 flux out of the air 2 equal flux into the yeast at the interface
  • BC4 no flux at the bottom of the well
  • This equation is very similar to the one obtained for the skin model. It can also demonstrate a direct relation to the oxygen consumption rate under the liquid bandage to the steady-state oxygen content of the liquid bandage. Accordingly, the model can serve as a good proof-of-concept for the functioning of the liquid bandage.
  • oxygen consumption models can be tested.
  • the oxygen consumption models developed for this experiment were yeast solutions of varying optical densities.
  • a yeast oxygen-consumption model offers an easier and more cost-effective alternative.
  • yeast undergo aerobic respiration, converting oxygen and carbohydrates into carbon dioxide and water.
  • Various solutions containing different amounts of yeast can be used, such that different rates of oxygen consumption can be observed as the yeast respire.
  • a first step in developing yeast oxygen consumption models can be to create sterile yeast extract, peptone, and dextrose (YPD) broth, which is a solution of yeast extract, peptone, and dextrose.
  • YPD is a commonly used growth media for maintaining cultures of S. cerevisiae yeast.
  • 50 g of YPD powder (Sigma-Aldrich Y135) may be dissolved in 1 L of distilled water then the solution can be autoclaved for 20 minutes. This YPD broth was cooled at room temperature.
  • yeast solutions a solution of 0.1 g of yeast in 10 mL of YPD broth in a 10 mL sterile tube can be made. Next, this initial solution can be diluated by 20, and then consecutive 2-fold dilutions can be performed to create 5 more yeast solutions. To characterize a yeast densities, light scattering can be used. Using a spectrophotometer, the maximum reading can be 2.5, and the dilutions that would give several solutions with readings below about 1.5 can be used. The solutions can be left at room temperature during a characterization experiments and later during the transportation to the imaging site as well as while imaging.
  • Oxygen consumption of each yeast solution can be assessed using a respiration chamber that measured the pO 2 of the yeast solutions as the organisms consumed oxygen from the solutions at a constant rate.
  • the assay was conducted in a small 4 mL respiration chamber that contained a small stir bar and a Clark-type oxygen electrode.
  • This electrode located at the base of the reaction chamber, consists of a platinum cathode and a silver-chloride anode.
  • An electrolyte solution can be placed over the tip of the electrode and prevented from diffusing into the reaction chamber by an oxygen-permeable Teflon membrane. Oxygen can diffuse across the membrane between the electrolyte solution and the yeast solution in the chamber. Voltage measurements can be transmitted to a computer and the data was collected using the PowerLab software. For each measurement, approximately 2 mL of yeast solution can be added. The solution can be taken up in a syringe, then air can be introduced through the stopcock to fill the syringe in order to oxygenate the solution.
  • the stopcock can then closed and the solution can be mixed thoroughly by swirling and tilting the syringe. This process oxygenates the solution, such that conditions are primed to observe oxygen consumption by the yeast immediately upon adding the yeast to the chamber.
  • the chamber can be rinsed with deionized water multiple times between measurements.
  • each yeast solution can be added to the chamber, time for the yeast to consume the oxygen can be allowed until the trace demonstrates a distinct constant slope.
  • the measurements can be recorded in terms of voltages by converting them to partial pressures of oxygen. To do so, two points with known oxygen contents can be used to calibrate measurements. So, the voltage can be measured when the chamber was empty (filled with air) and set that to be equal to an atmospheric pO2 at 25°C, which is 153 mmHg. For the second point, the plateau that the voltage reached once the yeast had consumed most of the oxygen can be used. This can be set to be equal to 3 mmHg because at this level, the yeast switch to fully anaerobic respiration and they can never fully deplete the oxygen in the solution.
  • FIG. 7B is a graph of the results of oxygen consumption rate measurements. Specifically, FIG. 7B shows a linear regression between the slope of the linear portions at the end of the curves in panel (a) and the optical density of the yeast solutions.
  • Figure 7A shows the pO2 values of the various yeast solutions changing with time.
  • the yeast solutions show a decrease in the amount of oxygen in the chamber with time.
  • the rate of decrease generally increases as the optical density (OD) of the solution increases as can be expected.
  • the rate of decrease of pO2 can be considered as the rate of oxygen consumption by the yeast. It is can also be significant to note that the solutions took only a short amount of time to reach a period at which the rate of oxygen consumption appears to be constant (indicated by constant slopes observed at later time points).
  • a correlation of each OD600 with the corresponding rate of oxygen consumption can be done, as seen from the strong linear negative correlation established in FIG. 7B.
  • OD600 can be an amount of light absorbed by the culture at a wavelength of 600 nm using a spectrophotometer.
  • yeast solutions of varying concentrations can be a good model of oxygen consumption and the rate of consumption can be easily determined by the measurement of the optical density of the solution using a spectrophotometer.
  • a liquid bandage and its formulation can be determined.
  • a solidified liquid bandage sealed over the top of wells in a plate containing yeast solutions can be used.
  • the plastic can be very sticky and stretchable.
  • a sample of oxyphor R4, coumarin 500, and liquid bandage in a 10: 1 : 10 ratio can be used.
  • trials with different formulations of oxyphor, coumarin, and liquid bandage on top can be done.
  • a sample of oxyphor R4 (200 uM), coumarin 500 (10 mM), and liquid bandage in a 10: 1:10 ratio can be combined in a small vial, and 5 ⁇ L of this mixture can be pipetted on top of each well. Imaging can be done for 6 minutes at 2-minute intervals and the average radiant efficiency in each well can be recorded and the average background noise can be subtracted.
  • FIGS. 8A-8C show data produced for a trial using 5 uL of a 10:1 : 10 mixture of liquid bandage, coumarin, and oxyphor R4 pipetted on top of the liquid bandage.
  • FIG. 8A shows a phosphorescence of oxyphor R4 averaged across all images at different time points plotted against OD600. The error bars are +/- 1 standard deviation (SD).
  • FIG. 8B shows a phosphorescence of time averaged oxyphor R4 phosphorescence normalized by time averaged coumarin phosphorescence averaged plotted against OD600.
  • FIG. 9C shows phosphorescence over time for each OD600 sample.
  • FIGS. 9A-9B shows data produced for a trial using coumarin 500 (0.24 ⁇ L), oxyphor (2.4 ⁇ L), and liquid bandage (2.4 ⁇ L) pipetted directly on top of the solidified liquid bandage.
  • FIG. 9A shows phosphorescence of oxyphor R4 averaged across all images at different time points plotted against OD600.
  • FIG. 9B shows phosphorescence of time averaged oxyphor R4 phosphorescence normalized by time averaged coumarin phosphorescence averaged plotted against OD600.
  • a larger volume (20 ⁇ L) can be used of only Oxyphor R4 in water on top of the solidified liquid bandage covering the wells.
  • the data from this trial can be visualized in FIGS. 10A and 10B.
  • a clear trend in which the emission increases as the optical density of the yeast solutions increases can be obtained. This may be because as the OD increases, the oxygen consumption rate increases. This may result in less oxygen in the bandage at equilibrium as described by the mathematical model. As a result, less oxyphore may be quenched and the emission may be greater.
  • the data can be transformed to show the intensity of emission as a function of the rate of oxygen consumption. Due to the linear relationship and the fact that a greater oxygen consumption rate is represented by a greater negative value, the plot can be simply a mirror image of the one as a function of OD.
  • the hyperbolic shape of this emission curve can agree with the prediction of the model.
  • a better proof of concept can be to compare it to the predicted curve but this may require knowingthe maximum emission of Oxyphore R4 for the Stem-Volmer equation, the diffusion coefficient of oxygen in the liquid bandage, and the thickness of the liquid bandage. Nevertheless, the lack of unreasonable assumptions in the model which agrees with the shape of this curve serves as a good proof-of- concept for the sensor.
  • FIGS. 10A and 10B show data produced for a trial using only oxyphor R4 pipetted on top of the liquid bandage.
  • FIG. 10A shows phosphorescence of oxyphor R4 averaged across all images at different time points plotted against OD600.
  • FIG. 10B shows fluorescence as a function of oxygen consumption rate, determined using the results from the yeast model characterization results to relate OD600 to oxygen consumption rate.
  • a liquid bandage can include an alginate hydrogel as an alternative to the liquid bandage.
  • Two formulations of the hydrogel can be CaS0 4 or CaCl 2 as the source of bivalent positive ions for crosslinking.
  • a base solution of 2% weight per volume of sodium alginate in deionized water can be used.
  • 0.435 g of CaS0 4 can be added to 50 mL of alginate solution with the goal of having the number of moles of calcium in the hydrogel equal half the moles of alginate monomers in the gel.
  • CaSO 4 may not dissolve easily in the alginate solutions so a large part of it settled to the bottom of the solution container.
  • the supernatant of the CaSO 4 hydrogel mixture can be poured off to form relatively homogeneous solutions that can be of an acceptable consistency for a liquid bandage material.
  • addition of CaCl 2 can resulted in crosslinking resulting in clumps in the solutions which may make it difficult to get a homogeneous gel.
  • an alginate hydrogel can include CaSO 4 having between 0.130mL to 0.520mL.
  • the alginate hydrogel can include CaCl 2 having between 0.5275mL to ImL.
  • the most promising hydrogel formulation was created by first completely dissolving 0.130 g of CaS0 4 in 10 mL of deionized water, then this can be mixed with 2% weight per volume of sodium alginate in deionized water in a 1 :1 ratio (resulting in a final solution with 1% w/v alginate).
  • This formulation formed a clear hydrogel that would be appropriate for imaging (FIG. 13).
  • this hydrogel formulation may be characterized in order to take phosphorescence readings using Oxyphor R4 incorporated into the hydrogel.
  • a paint-on liquid bandage embedded with oxygen-sensitive metalloporphyrins can offer capabilities as a transcutaneous device for tracking skin injury. The ability to develop these sorts of responsive bandages will ultimately improve patient care and the treatment of peristomal skin injuries.
  • the liquid bandage solution mav not be miscible with water, but the Oxyphor R4 may only be available in aqueous solutions.
  • the bandage could be composed of an alginate-based hydrogel embedded with oxyphors.
  • the alginate hydrogel proves technically infeasible due to compatibility or degradation concerns, other embodiments could seek to utilize different components.
  • Oxyphor R4s could either be purchased out of solution, isolated from the aqueous solution, or dissolved in ethanol as the solvent.
  • the NEW-SKIN ® liquid bandage other liquid bandage formulations with fewer hydrophobic elements can be used.
  • alginate hydrogel is a suitable option, a water-soluble control dye can be used.
  • Coumarin 500 does not dissolve in water, but the typical solvent for Coumarin 500, ethanol, appeared to react with alginate. Therefore, neither ethanol nor water may be used in alginate hydrogels with coumarin.
  • the use of alginate hydrogels may require the identification and purchase of a water soluble dye to replace Coumarin 500.
  • measurements of oxygen diffusivity in the final liquid bandage, maximum oxyphore emission, and thickness of the bandage may allow a more complete proof-of-concept.
  • FIG. 11 shows a method 1100 for detecting peristomal skin injury.
  • the method may be applied to a computing device such as a wearable device, mobile device, personal computer or server.
  • the wearable device may include the light sensor unit 216, the sensor interface 218, and the computing unit 220.
  • the wearable device can output light pulses, through a light output device, onto a wearable sensor mounted on peristomal skin.
  • the wearable sensor may include phosphorescent metalloporphyrin molecules that are excited by pulses of light based on oxygen consumption.
  • the wearable sensor may be a liquid bandage that is painted on a user’s abdomen near a stoma. The liquid bandage, once dry, can output phosphorescence when exposed to light pulses.
  • the wearable device can obtain phosphorescence intensity levels of the phosphorescent metalloporphyrin molecules excited by the pulses of light.
  • the wearable device trough, for example, a phosphorimeter can detect phosphorescence and calculate phosphorescence intensity levels.
  • the wearable device can determine a peristomal skin injury based on the phosphorescence intensity levels.
  • the wearable device for example, can use the phosphorescence intensity levels to determine oxygen consumption levels under the wearable sensor.
  • the oxygen consumption levels can include an oxygen consumption rate that can be used to determine a peristomal skin injury.
  • FIG. 12 shows a computing system 1200 that can be part of the system 200 for detecting a peristomal skin injury.
  • the computing system 1200 can include a computing environment 1210, a user interface 1250, a communication unit 1260.
  • the computing system can further include a haptic motor and an accelerometer.
  • the computing environment 1210 can include a processor 1220, a memory 1230, and an I/O interface 1240.
  • the computing environment 1210 can be coupled to the user interface 1250 and communication unit 1260 through the I/O interface 1240.
  • the processor 1220 can typically control the overall operations of the computing environment 1210, such as the operations associated with data acquisition, data processing, and data communications
  • the processor 1220 can include one or more processors to execute instructions to perform all or some of the steps in the above-described methods.
  • the processor 1220 can include one or more modules that facilitate the interaction between the processor 1220 and other components.
  • the processor may be or include a central processing unit (CPU), a microprocessor, a single chip machine, a graphical processing unit (GPU) or the like.
  • the memory 1230 can store various types of data to support the operation of the computing environment 1210.
  • Memory 1230 can include predetermined software 1231. Examples of such data comprise instructions for any applications or methods operated on the computing environment 1210, raw data, detected data, oxygen levels, phosphorescence intensity levels, light levels, etc.
  • the memory 1230 may be implemented by using any type of volatile or non-volatile memory devices, or a combination thereof, such as a static random-access memory (SRAM), an electrically erasable programmable read-only memory (EEPROM), an erasable programmable read-only memory (EPROM), a programmable read-only memory (PROM), a read-only memory (ROM), a magnetic memory, a flash memory, a magnetic or optical disk.
  • SRAM static random-access memory
  • EEPROM electrically erasable programmable read-only memory
  • EPROM erasable programmable read-only memory
  • PROM programmable read-only memory
  • ROM read-only memory
  • magnetic memory
  • the I/O interface 1240 can provide an interface between the processor 1220 and peripheral interface modules, such as a RF circuitry, external port, proximity sensor, audio and speaker circuitry, video and camera circuitry, microphone, accelerometer, display controller, optical sensor controller, intensity sensor controller, other input controllers, keyboard, a click wheel, buttons, and the like.
  • the buttons may include but are not limited to, a home button, a power button, and volume buttons.
  • the user interface 1250 can include a speaker, lights, display, haptic feedback motor or other similar technologies for communicating with the user.
  • Communication unit 1260 provides communication between the processing unit, an external device, mobile device, and a webserver (or cloud).
  • the communication can be done through, for example, WIFI or BLUETOOTH hardware and protocols.
  • the communication unit 1260 can be within the computing environment or connected to it.
  • non-transitory computer-readable storage medium comprising a plurality of programs, such as comprised in the memory 1230, executable by the processor 1220 in the computing environment 1210, for performing the above- described methods.
  • the non-transitory computer-readable storage medium may be a ROM, a RAM, or the like.
  • the non-transitory computer-readable storage medium has stored therein a plurality of programs for execution by a computing device having one or more processors, where the plurality of programs when executed by the one or more processors, cause the computing device to perform the above-described method for motion prediction.
  • the computing environment 1210 may be implemented with one or more application-specific integrated circuits (ASICs), digital signal processors (DSPs), digital signal processing devices (DSPDs), programmable logic devices (PLDs), field-programmable gate arrays (FPGAs), graphical processing units (GPUs), controllers, micro-controllers, microprocessors, or other electronic components, for performing the above methods.
  • ASICs application-specific integrated circuits
  • DSPs digital signal processors
  • DSPDs digital signal processing devices
  • PLDs programmable logic devices
  • FPGAs field-programmable gate arrays
  • GPUs graphical processing units
  • controllers micro-controllers, microprocessors, or other electronic components, for performing the above methods.

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Abstract

L'invention concerne un système et un procédé de détection des niveaux d'oxygène qui indiquent une lésion cutanée péristomiale, d'autres lésions cutanées ou une cicatrisation. Le système peut comprendre un capteur à porter sur soi. Le capteur à porter sur soi peut comprendre des molécules de métalloporphyrine phosphorescente qui sont excitées par des impulsions de lumière sur la base de la consommation d'oxygène. Le système peut également comprendre un capteur de lumière. Le capteur de lumière peut détecter la phosphorescence à partir du capteur à porter sur soi. Le système peut en outre comprendre une unité de calcul. L'unité de calcul peut détecter une lésion cutanée péristomiale sur la base de la phosphorescence détectée.
PCT/US2023/064228 2022-03-14 2023-03-13 Système et procédé de détection d'oxygène pour la prédiction, la détection, l'atténuation et/ou la prévention d'une lésion cutanée péristomiale WO2023178034A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6362175B1 (en) * 1991-09-20 2002-03-26 The Trustees Of The University Of Pennsylvania Porphyrin compounds for imaging tissue oxygen
EP3019854B1 (fr) * 2013-07-10 2021-01-06 The General Hospital Corporation Composés, systèmes et procédés pour surveiller et traiter la surface d'un sujet

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6362175B1 (en) * 1991-09-20 2002-03-26 The Trustees Of The University Of Pennsylvania Porphyrin compounds for imaging tissue oxygen
EP3019854B1 (fr) * 2013-07-10 2021-01-06 The General Hospital Corporation Composés, systèmes et procédés pour surveiller et traiter la surface d'un sujet

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LI ZONGXI ET AL: "Sensing, monitoring, and release of therapeutics: the translational journey of next generation bandages", JOURNAL OF BIOMEDICAL OPTICS, SPIE, 1000 20TH ST. BELLINGHAM WA 98225-6705 USA, vol. 24, no. 2, 1 February 2019 (2019-02-01), pages 21201, XP060137964, ISSN: 1083-3668, [retrieved on 20181227], DOI: 10.1117/1.JBO.24.2.021201 *

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