Method and sensor for obtaining layer-specific properties of tissue layers

Abstract

A non-invasive method of and sensor (14) for obtaining layer-specific properties of tissue layers (13, 15, 17) comprising an outer layer (13) and underlying layers (15, 17) The vibroacoustic sensor (14) being placed in responsive contact with an outer surface (18) of the outer layer (13) of the tissue layers (13, 15, 17). Activating the vibroacoustic sensor (14) creates vibratory motion at the outer surface (18) of the outer layer (13), thereby generating vibroacoustic waves through all layers. The generated vibroacoustic waves being detectable by the vibroacoustic sensor (14) to generate output data, which is used to generate a phase velocity dispersion curve. Layer-specific properties of each tissue layer (13, 15, 17) are obtained by analysing discontinuities in the phase velocity dispersion curve, where the discontinuities represent boundaries between tissue layers.

Description

[0001] Method and Sensor for Obtaining Layer-Specific Properties of Tissue Layers Field of Invention

[0002] The invention relates to a non-invasive method of and vibroacoustic sensor for obtaining layerspecific properties of tissue layers e.g., skin comprising an outer layer and underlying layers.

[0003] Background to the invention

[0004] Skin is a complex 3D, multi-layer, composite tissue structure that comprises the epidermis (cellular layer and protective outer barrier, 100-200 / ini), the dermis (fibrous mesh structural layer, 1-2 mm) and the hypodermis (insulating layer used for energy storage and skin to muscle connections, >2 mm). Within these layers there are also a multitude of other structures including blood vessels, nerve endings, hair follicles, lymphatic vessels, varying cellular subsets and may more.

[0005] During physiological processes either due to normal health changes or disease, it will be appreciated the biological changes which manifest concurrently affect the mechanical characteristics e.g., elasticity, viscosity and thickness of skin. For example, in dermatological conditions, such as eczema or psoriasis, the epidermal layer becomes inflamed, affecting the overall layer material elasticity, layer thickness and fluid content. Similarly, the reddening and swelling of the dermis during the immune inflammation of chronic wounds marks both a biological and material change of the layer.

[0006] Purely surface-based assessment, such as visual examination or physical palpation, fails to identify and understand tissue changes in the affected dermis and hypodermis. This heavily impacts a clinician’s ability to effectively treat a patient. Similarly, many assessment methods (e.g., the EczemaArea Severity Index) fail to account for the variations in disease presentation in aged skin or in skin that is tattooed or pigmented.

[0007] Chemical, electrical, and mechanical approaches have been shown to detect changes in tissue health on a superficial (epidermal) level. However, due to the nature of progression formany skin diseases, the superficiality of measurement may not be sufficient for the early detection or monitoring of many conditions, such as chronic conditions.

[0008] Ultrasound systems show some application in skin disease appraisal and monitoring. However, progress is hindered by the propagation depth and resolution of high frequency acoustic waves. High frequency ultrasound provides a much lower wavelength than low-frequency, ultrasound techniques thereby enabling better resolution and lower depth of measurement. However, the analysis of the skin i.e., a thin-layered complex structure results in heavy wave scattering, which impacts a clinician’s ability to identify problems and effectively treat a patient. It also still has a lower resolution than that needed for skin-layer measurements (i.e. micro-level). Where high frequency elastography has been proposed, the equipment complexity is high and resolution is more suited to larger structures such as tumour detection. Optical coherence tomography (OCT) is an imaging modality that provides an imaging depth and resolution between the bounds of conventional ultrasound devices and confocal microscopy. Much like ultrasound systems, OCT allows for real-time, in situ visualisation of tissues. However, conventional OCT systems such as the Telesto™ series utilise large pieces of equipment, limiting the portability of the device. Additionally, to acquire high resolution three-dimensional scans of a tissue site, long acquisition times are required with complex post-hoc image processing used to enhance microstructural visualisation.

[0009] Ultrasound elastography (USE) is a non-invasive imaging technique that can be used to measure mechanical properties of the superficial layers of the skin. For example, by monitoring the response of tissue to acoustic energy, the mechanical properties measured are stiffness or elasticity.Summary of the Invention

[0010] The present invention provides a non-invasive method of obtaining layer-specific properties of tissue layers comprising an outer layer and underlying layers, the method comprises: placing a vibroacoustic sensor in responsive contact with an outer surface of the outer layer of the tissue layers,

[0011] activating the vibroacoustic sensor to create vibratory motion at the outer surface of the outer layer, thereby generating vibroacoustic waves through all layers;

[0012] detecting the generated vibroacoustic waves with the vibroacoustic sensor thereby generating output data;

[0013] generating a phase velocity dispersion curve using the output data;

[0014] analysing discontinuities in the phase velocity dispersion curve with a mathematical model to obtain layer-specific properties of each tissue layer, wherein the discontinuities represent boundaries between tissue layers.

[0015] The analysing step may comprise applying the mathematical model consecutively to the discontinuities in the phase velocity dispersion curve to obtain layer-specific properties of each tissue layer, wherein the discontinuities represent frequency regions associated with each tissue.

[0016] Applying the mathematical model may comprise applying a first mathematical model to the frequency region associated with the outer layer and obtaining layer specific properties of the outer layer and subsequently applying a further mathematical model to the frequency region associated with each underlying layer consecutively utilising data obtained from a previous layer in analysing each subsequent layer.

[0017] The first mathematical model may be a homogeneous shear wave mathematical model.Surface-acoustic wave interpretation may be used to supplement interpretation of the outer layer properties obtained from the homogeneous shear wave model.

[0018] The first mathematical model may determine shear elasticity and shear viscosity characteristics of the outer layer.

[0019] The further mathematical model may be a heterogeneous shear wave model.

[0020] The heterogenous wave model may be expressed by equation:

[0021]

[0022] wherein Cs(") isadata set of estimated wave velocities for a variety of tested frequencies, a> is the angular frequency, p is material density, n is a number associated with the tissue layer being analysed, wherein n = 2 is a first layer directly underlying the outer layer and n = 3, n= 4 etc. are underlying layers counted consecutively from the first underlying layer.

[0023] The layer specific properties of each tissue layer may be determinable when properties of an overlying layer is known, wherein the first underlying layer properties are determinable after determining the outer layer properties, a second underlying layer properties are determinable after determining the first underlying layer properties and so on until properties of all tissue layers are determined.

[0024] The present invention further provides a vibroacoustic sensor configured to be placed or worn in responsive contact with tissue layers comprising an outer layer and underlying layers, wherein the vibroacoustic sensor is operable to non-invasively actively monitor / measure properties of the outer layer and the underlying layers, the vibroacoustic sensor comprising:

[0025] at least one vibratory source; andat least one receiver displaced relative to the at least one vibratory source,

[0026] wherein the at least one vibratory source is operable to create vibratory motion to an outer surface of the outer layer, thereby generating vibroacoustic waves through all layers; and wherein the at least one receiver is operable to detect the vibroacoustic waves and provide collectable output data, which output data being configured for analysis to determine layerspecific properties of each tissue layer.

[0027] The vibroacoustic sensor is configured to objectively discern between healthy and wounded or diseased tissue e.g., skin.

[0028] The use of such a device enables tracking the progression of skin diseases, systemic conditions that evoke a change in skin material properties, or the effects of a healing wound on the skin layers proximate to the wound. The device allows for non-invasive monitoring and allows for the device to be used in a clinical setting, a non-clinical healthcare support environment (e.g. a pharmacy) or more conveniently allows for use by the patient at home. The device being configured to be in responsive contact with an outer surface of the user’s skin relates to avoiding movement of the sensor relative to the skin. This ensures that the data collected from the receivers is not contaminated. In this regard, the only movement related to the sensor is local displacement of the vibratory source to create a displacement / vibration at the skin surface to generate vibration and resulting vibroacoustic waves through the layers of skin.

[0029] The at least one vibratory source and the at least one receiver may be piezoelectric transducers.

[0030] The vibroacoustic sensor may include two receivers per single associated vibratory source, wherein each receiver is spaced from the associated vibratory source, and the receivers are also spaced from each other.The receivers may each be displaced about a longitudinal axis of the associated vibratory source and about a transverse axis of the associated vibratory source.

[0031] Each receiver may be displaced by between 1mm and 10mm relative to a longitudinal axis of the associated vibratory source and relative to a transverse axis of the associated vibratory source and relative to each other. For example, both the receivers may be displaced 5mm from each side of the transverse axis of the associated vibratory source. Alternatively, one receiver may be displaced 5mm and the other receiver may be displaced 7mm from the associated vibratory source to an opposite side of the transverse axis of the vibratory source. The at least one vibratory source may provide local vibration to the outer surface of the outer tissue layer at a frequency between 0.1 to 20 kHz.

[0032] Composition of the vibroacoustic sensor may include film layers supporting the at least one vibratory source and the at least one receiver.

[0033] The composition may further comprise conformable electrodes, wherein respective conformable electrodes are attached to each of the at least one vibratory source and the at least one receiver.

[0034] The film layers may support the conformable electrodes. The electrodes may be sandwiched between two film layers.

[0035] The sensor may further comprise an adhesive layer operable to support and protect the vibratory source and receivers. The sensor may further comprise encapsulation operable in use to encapsulate / house the at least one vibratory source and the at least one receiver. The adhesive layer may be positioned below the film layers. The encapsulation may be positioned above the film layers.

[0036] Where both an adhesive layer and encapsulation are included, the combination of the adhesive layer and the encapsulation houses the at least one vibratory source, the at least one receiver and the electrodes therebetween.The adhesive layer is operable to semi-permanently adhere the vibroacoustic sensor to an outer surface of the outer tissue layer. Alternatively, or in addition to the adhesive layer, the sensor may further comprise a strap or the like configured to adjustably and temporarily attach the sensor to the outer surface of the outer layer of the tissue layers. Alternatively, the sensor may be included as part of a handheld device.

[0037] In each of these examples static contact between the vibroacoustic sensor and the tissue can be achieved. In the example using adhesive, the adhesive adheres the sensor directly to the outer surface of the outer layer thereby creating immovable / static contact. In the example utilising a strap or the like allows for the vibroacoustic sensor to be applied to the outer surface and adjustment via the strap or the like ensures the sensor is pressed against the outer surface thereby creating immovable / static contact between the sensor and the outer surface of the tissue layers. In the example using a handheld device the sensor can be pressed against the outer surface of the tissue layers and the force applied via the handheld device ensures immovable / static contact between the outer surface of the tissue layers and the sensor component of the handheld device.

[0038] The film layers may be made from flexible polymers. For example, polyetherimide (PEI), polyamide, mylar®, silicones etc.

[0039] The film layers may be made from polyetherimide (PEI) film.

[0040] The electrodes may be made from conductive material coated flexible polymers.

[0041] The electrodes may be made from metal coated PEI film.

[0042] The electrodes may be made from gold coated PEI.

[0043] The at least one vibratory source and at least one receiver may be incorporated in a smart device. The smart device may be wearable. The smart device may be configured to be remotely operable and accessible. The at least one vibratory source and at least one receiver may be incorporated in a handheld device, which is operable to press the one vibratory sourceand at least one receiver into contact with the outer layer. The smart device may be incorporated in a handheld device. The handheld device may be configured for remote operation and access. Remote operation and access allows for remote analysis and less frequent clinic time.

[0044] Each of the film layers, the base layer, the adhesive layer and the encapsulation layer may be between 50 pm to 2mm thick.

[0045] The encapsulation layer may be made from a flexible polymer material. For example, the encapsulation layer may be made from EcoFlex®.

[0046] The adhesive layer may be made from a soft elastomer. For example, the adhesive layer may be made from S3-PDMS™.

[0047] These materials are suitable because the vibroacoustic sensor will be under low strain after attachment to the skin and allow better engagement of the sensor to the outer layer of tissue e.g., skin.

[0048] The sensor may further comprise a water release layer over the encapsulation layer. The water release layer aids attachment of the sensor to the outer layer e.g., skin. The water release layer acts like a “temporary tattoo”.

[0049] Description of Drawings

[0050] Fig. 1A illustrates a representation of a vibratory source and two receivers mounted on the surface of layered material, such as skin;

[0051] Fig. 1B illustrates a graphical representation of acoustic waves detected by a receiver of Fig.

[0052] 1A;

[0053] Fig. 1C illustrates an arrangement of a vibratory source and two receivers as applied to the vibroacoustic sensor of Fig. 2A and 2B;Fig. 2A illustrates an example of an exploded view of a wearable vibroacoustic sensor, which includes a vibratory source and two receivers, film layers, a substrate layer, an adhesive layer and encapsulation;

[0054] Fig.2B represents an assembled vibroacoustic sensor including the components illustrated in Fig. 2A in a stacked form;

[0055] Fig. 3 illustrates a graphical representation of human skin composition;

[0056] Fig. 4A illustrates a phase velocity dispersion curve, which is representative of skin layer properties by use of the sensor illustrated in Fig. 2A and 2B;

[0057] Fig. 4B illustrates a simplified representation of skin layer distribution that corresponds with the layer changes in Fig. 4A; and

[0058] Fig.5A illustrates an example of a wristband device incorporating components of the vibroacoustic sensor as illustrated in Fig. 2A and 2B;

[0059] Fig. 5B illustrates an example of a handheld device incorporating components of the vibroacoustic sensor as illustrated in Fig. 2A and 2B;

[0060] Fig. 6A shows a comparison of healthy skin (1) alongside skin affected by eczema (2) and skin affected by psoriasis (3);

[0061] Fig. 6B shows a graphical comparison of sensor measurements of characteristics of the epidermis and dermis at two sites of skin affected by eczema compared with healthy skin; Fig. 7A illustrates a graphical representation of changes in blood flow at the epidermis; and Fig. 7B illustrates a graphical representation of changes in blood flow at the dermis.

[0062] Description

[0063] Fig. 1A illustrates an example of a vibratory source 10 and two receivers 12A, 12B, applied to an outer surface 18 of a layered medium 20 e.g. a user’s skin. The vibratory source 10 andtwo receivers 12A, 12B are examples of the functional components of a vibroacoustic sensor 14 as illustrated in exploded form in Fig. 2A and assembled form in Fig. 2B.

[0064] An example of how the vibratory source 10 and the receivers 12A, 12B are applied to the user’s skin, as a wearable is described further below with reference to Fig. 2A and Fig. 2B. The vibratory source 10 and receivers 12A and 12B can be incorporated as part of handheld device 100, as described further below with reference to Fig. 5.

[0065] As noted above, the skin 20 is a complex 3D, multi-layer, composite tissue structure (see Fig.

[0066] 3) that comprises the epidermis 13 (cellular layer and protective outer barrier, which is 100-200 zm thick), the dermis 15 (fibrous mesh structural layer, which is 1-2 mm thick) and the hypodermis 17 (insulating layer used for energy storage and skin to muscle connections, which is >2 mm thick).

[0067] Referring again to Fig. 1A, IBand 1 C, the vibratory source 10 is configured to provide an input stimulus i.e. , a displacement 9 at the surface 18 to generate a localised vibration / pulse 16 at the surface 18 and through the skin layers 13, 15, 17. The vibration / pulse 16 causes vibroacoustic waves / perturbations to propagate through the skin layers. These material perturbations propagate as acoustic waves 22 under the skin surface 18, through and along the skin layers 13, 15, 17.

[0068] The perturbations create strain in each of the piezoelectric receivers 12A, 12B. The receivers 12A, 12B, also located on the skin surface 18, therefore being configured to detect the acoustic waves 22 and facilitate generating a functionally related output. As described further below, the output from the receivers is captured and manipulated to be presented in a numerical or graphical form (see Fig. 1B and Fig. 4A). The output relating to the mechanical characteristics of each skin layer 13, 15, 17 (see Fig. 4A).

[0069] The extent and characteristics of the acoustic waves 22 generated will be affected by the different characteristics of each skin layer 13, 15, 17. The receivers 12A and 12B are locatedsuch as to determine a comparative acoustic wave output to therefore provide information characteristic of the different properties of the different skin layers.

[0070] The placement of the receivers 12A, 12B relative to the vibratory source 10 is such that each receiver 12A, 12B detects the acoustic waves 22 generated through the skin layers 13, 15, 17. In the illustrated example the two receivers are arranged, relative to the vibratory source 10, such that each receiver 12A, 12B is longitudinally displaced X1, Az and transversely displaced X2, X3 from the vibratory source 10 and relative to each other, as illustrated in Fig.

[0071] 1C.

[0072] In the illustrated examples, the vibratory source 10 and the receivers 12A, 12B are provided by piezoelectric elements.

[0073] In the examples shown in Fig. 1C and Fig. 2B, the vibratory source 10 is a piezoelectric element of 10mm by 4mm (shown as a rectangle) and the receivers 12A, 12B are piezoelectric elements of 2mm by 2mm (shown as squares). The first receiver 12A is displaced around 5mm (X2) from the transverse axis 19 of the vibratory source 10 and the second receiver 12B is displaced approximately 7mm (X3) from the transverse axis 19 of the vibratory source 10. In this example, the first receiver 12A is displaced between 1mm and 10mm (X1) from the longitudinal axis 21. The second receiver 12B is displaced a distance Az e.g., between 1mm and 8mm from the first receiver 12A. Az is utilised to calculate the velocity of the moving vibroacoustic waves. The velocity is used as data and plotted in graphical form as illustrated in FIG 4A. Using the stress-voltage duality of piezoelectric elements, it is possible to supply an AC voltage to the vibratory source 10 to create the displacements / vibration 9 / 16 at the surface 18 and the material perturbations through the skin layers 13, 15, 17. The resulting vibroacoustic waves 22 that occur through and along the skin layers 13, 15, 17 create strain in each of the piezoelectric receivers 12A, 12B; the strains creating the piezo electric effect enables a signal output. Taking account of a time lag due to the viscous component of thesoft skin tissue the signal output is used to calculate the wave velocity, which as noted above is the data plotted as the Y-axis in the results displayed graphically in Fig. 4A.

[0074] Fig. 2A illustrates an exploded view of a wearable vibroacoustic sensor 14 in accordance with an embodiment of the present invention. The vibroacoustic sensor 14 as described further below represents a non-invasive device that can be used to monitor changes in skin layer characteristics of injured, damaged or even supposedly healthy skin e.g. where there is a non-visible underlying condition.

[0075] The illustrated example includes the vibratory source 10 and two receivers 12A, 12B mounted on a first film layer 24, which also supports first electrode arms 26. A first end of each of the first electrode arms 26 is connected to a respective one of the vibratory source 10 and the two receivers 12A, 12B.

[0076] A second film layer 28 is included. The second film layer 28 supports second electrode arms 30 associated with each of the vibratory source 10 and the receivers 12A, 12B. A first end of each of the second electrode arms 30 is also connected to a respective one of the vibratory source 10 and the two receivers 12A, 12B.

[0077] In an assembled form (see Fig. 2B), the vibratory source 10 and the two receivers 12A, 12B are sandwiched between the two film layers 24, 28 and the first ends of the associated electrodes arms 26, 30.

[0078] The film layers 24, 28 act as a flexible substrate to support the vibratory source 10, the receivers 12A, 12B and the associated electrodes 30.

[0079] The illustrated vibroacoustic sensor 14 is designed to be attached to the user’s skin such that the sensor is responsive / conformable to the user’s skin surface 18.

[0080] In the example illustrated in Fig. 2A and 2B, an adhesive layer 34 is included. The adhesive layer 34 is adhered to the flexible substrate 24 and in use provides an interface that facilitates attaching the sensor 14 in an immovable and static manner to the skin surface 18.The adhesive layer 34 facilitates semi-permanent, direct, adhesion of the assembled vibroacoustic sensor 14 to the user’s skin surface 18.

[0081] The substrate layers 24, 28 and the adhesive layer 34 are selected to ensure conformability of the vibroacoustic sensor 14 with the user’s skin 18 and to ensure that actuation by the vibratory source 10 and responsiveness of the receivers 12A, 12B is not diminished.

[0082] Flexibility / malleability of the supporting Iayers24, 28, 34 is important to ensure that contact between the skin surface 18 and the vibratory source 10 and receivers 12A, 12B is maintained during testing / monitoring.

[0083] An encapsulation layer 32 is included. The encapsulation layer 32 serves to protect and secure, the vibratory source 10, the receivers 12A, 12B, the film layers 24, 28 and the electrode arms 26, 30 relative to the adhesive layer 34 when the components are compiled in a stack to form the vibroacoustic sensor 14.

[0084] A water release layer 36, is included in the exploded view of Fig. 2A, the water release layer aids attachment of the sensor 14 to the user’s skin. This layer 36 acts like a “temporary tattoo” where placement is achieved by covering the sensor 14 in a paper towel soaked in warm water. In assembling the sensor 14, the encapsulation layer 32 is added to the water release layer 36.

[0085] In the sensor 14 illustrated in Fig. 2A and 2B each of the substrate film layers 24, 28, the adhesive layer 34, the encapsulation layer 32 and the water release layer 36 are formed from malleable and complaint materials, for example flexible polymers. Each layer is thin, for example each layer has thickness between 50 pm to 2mm.

[0086] In the illustrated example, the encapsulation layer 32 is made from a polymer material e.g., EcoFlex®.The film layers 24, 28 and the electrode arms are made from flexible polymers, for example, polyetherimide (PEI), polyamide, mylar®, silicones etc. In this example polyetherimide (PEI) film is used.

[0087] The adhesive layer 34 is made from a soft, compliant i.e. , stretchy and sticky elastomer e.g., S3-PDMS, which is a polydimethylsiloxane-based elastomer. This ensures good adhesion of the sensor 14 to the skins surface and does not affect responsiveness of the sensor 14 when attached to the skin because the vibroacoustic sensor 14 will be under low strain after attachment to the skin.

[0088] This combination of materials ensures conformability of the skin surface 18 and the components of the sensor 14 is maintained during testing / monitoring.

[0089] Enhanced conformability is achieved when the components of the sensor 14 are contained within the polymer encapsulation layer e.g. Ecoflex®, and when the sensor 14 includes the adhesive layer e.g., S3-PDMS to adhere the vibroacoustic sensor 14 to the skin surface 18. In the illustrated example, an assembly of the first and second film layers 24, 28 with their respective electrode arms 26, 30 are formed from 70 to 75 pm thick PEI film. The sensing elements (vibratory source 10 and receivers 12A, 12B) are sandwiched between the two film layers 24, 28.

[0090] In this example, the electrodes arms 26, 30 facilitate connection of the vibratory source 10 and the receivers 12A, 12B to external equipment. The electrode arms 26, 30 include copper terminals 26T, 30T to appropriately connect the sensor 14 to the external ancillary equipment (not shown). When connected the electrode arms 26, 30 and terminals 26T, 30T facilitate displacement of the skin surface 18 via the vibratory source 10 and data collection as sensed by the receivers 12A, 12B; the data collected relating to the skin layer response to the displacement / vibration.The electrodes arms 26, 30 are thin (less than 70 pm thick) and flexible, but due to their function (connecting the vibratory source 10 and the receivers 12A, 12B to external equipment) it is important that the electrode arms 26, 30 are also tear resistant.

[0091] The shape of the electrodes may promote tear resistance. For example, the risk of tearing can be reduced by building in an element of compliance, e.g., a non-linear, curved or serpentine shape. This is desirable because the electrodes are connectable to external equipment (described above and further below).

[0092] In addition, or alternative to shape, the material composition of the electrodes 26, 30 may promote tear resistance.

[0093] In the illustrated example, the electrodes 26, 30 are manufactured from gold coated polyetherimide (PEI) film. The layer of gold applied to the PEI film is approximately 200 nm thick.

[0094] The combination of PEI and gold was found to be biologically compatible, tear and fracture resistant during manufacture, manipulation i.e. , when attaching the sensor to the user’s skin surface 18 and in use when the electrode terminals 26T, 30T are connected to external equipment.

[0095] The combination of the PEI film layers 24, 28 and the gold coated PEI film electrodes 26, 30 ensures compatibility of the film layers 24, 28 and the electrode arms 26, 30 and provides a conformable and tear resistant electrode design that can withstand multiple uses without incurring damage.

[0096] The electrodes are attached to the PEI film layers 24, 28 with a suitable adhesive e.g. cyanoacrylate.

[0097] In the illustrated example, the PEI film layers 24, 28 each include an outer support ring 40, 42 to provide support for the terminal end 26T, 30T of the electrode arms 26, 30. One of filmlayers 24 includes a central support section 24A that is configured to support and protect the vibratory source 10 and the receivers 12A, 12B and the electrode arms 26, 30.

[0098] Excess material is removed from both film layers 24, 28 to reduce non-compliance of the film layers 24, 28 and to limit vibroacoustic propagation / noise through the film layers 24, 28 when the sensor 14 is attached to the skin surface 18 for testing / monitoring.

[0099] To determine the properties of the skin layers the vibroacoustic sensor 14 is placed in conformable contact with the user’s skin surface. Conformable contact is provided by one of:

[0100] • adhesion of the sensor 14 to the skin surface 18 (Fig. 2B);

[0101] • attaching the sensor 14 into contact with the skin surface 18 (Fig. 5A); or

[0102] • pressing the sensor 14 into contact with the skin surface 18 (Fig. 5B).

[0103] Fig.5A illustrates an example of a wristband device 100 incorporating at least the vibratory source 10 and receiver components 12A, 12B of the vibroacoustic sensor 14 described above, with reference to Fig. 2A and 2B.

[0104] Fig.5B illustrates an example of a handheld device 110 incorporating at least the actuator and receiver components of the vibroacoustic sensor 14 described above, with reference to Fig.

[0105] 2A and 2B.

[0106] Regardless of how the vibroacoustic sensor 14 makes contact with the skin surface 18 it is important that the vibroacoustic sensor 14 is responsive to the vibroacoustic waves 22 generated through the skin.

[0107] The vibroacoustic sensor 14 as described and illustrated is capable of objectively quantifying the elastic / viscoelastic properties of soft tissues i.e., human skin. In contrast, purely visual examination or physical palpation, fail to identify nor have the sensitivity to understand tissue changes in the affected skin’s epidermis, dermis and hypodermis. This heavily impacts a clinician’s ability to effectively treat a patient.The vibracoustic sensor 14, as described and illustrated, is configured to use low-frequency (0.1-20 kHz) vibrations to map the velocity profile of the skin layers 13, 15, 17. Because the sensor utilises sub 20 kHz frequency, this allows the use of small and inexpensive piezoelectric elements for the vibratory source 10 and the receivers 12A, 12B. In contrast, ultrasound typically utilise vibroacoustic waves of frequency in the order of 2-12 MHz During testing of a vibroacoustic sensor 14 as described and illustrated, phase velocity dispersion curves (PVDC) were used to capture and present the results. An example PVDC is illustrated in Fig. 4A. From the distribution of data discontinuities 56, 58 are evident. The discontinuities represent boundaries between layers 50, 52, 54 as represented by the layered configuration shown in Fig. 4B.

[0108] The following equation represents one approach for a heterogeneous shear wave model, which when applied to the dispersion curve of Fig. 4A allows layer specific properties to be extracted.

[0109]

[0110] In the equation, Cs(&)) is the data set of estimated wave velocities for a variety of tested frequencies, co is the angular frequency and p is the material density.

[0111] In the equation “n” represents the layer being analysed e.g., n = 2 represents the second layer. For each layer, considered consecutively, the analytical method remains the same:

[0112] First, the single-layer (layer 1) homogenous model is applied to the uppermost dispersion curve in the PVDC to obtain the shear elasticity and shear viscosity of the upper layer;• Next, we move to the frequency region in the dispersion curve where we are propagating through the two uppermost layers. Here, n = 2 in the equation using the extracted upper layer values of layer 1.

[0113] • This process is repeated for increasing numbers of layers, where n = 3, 4, 5 etc. until all layers are tested.

[0114] The equation can be used to solve a dispersion curve where the unknown variables relate to a single layer, i.e., the properties of a third layer can only be found when the properties of the second layer are known. Therefore, layer properties should be considered consecutively. This analytical model is capable of extracting layer specific mechanical properties from surface driven vibroacoustic propagation. Models such as a surface-acoustic-wave interpretation may also be used to supplement the interpretation where an upper material layer may need to be interpreted by a Surface Acoustic Wave analysis prior to applying the heterogeneous shear wave model to lower layers.

[0115] Vibroacoustic measurements are widespread in non-medical and medical fields, yet their utility for monitoring changes in skin is limited by constraints in penetration depth and resolution. Furthermore, current non-vibroacoustic methods for skin-based measurements in clinical medicine often rely on subjective assessment protocols, such as visual examination and physical palpation, which only capture surface-level changes in tissue.

[0116] It is considered that utilisation of the vibroacoustic sensor 14 together with the analytical heterogeneous shear wave model described above could be used extensively in the clinical field of skin disease assessment and monitoring. This allows extraction of different properties of the tissue / skin layers. The ability to track the intrinsic changes of individual tissue layers has the potential to mitigate current physician biases, diagnostic uncertainty and variabilities. A further model, a surface acoustic wave model, can be used with the output from the vibroacoustic sensor 14, where the surface acoustic wave model allows representation of the sensor output in respect of the top few microns of the skin.The example described above with reference to Fig. 1 A, 2A and 2B relates to the vibroacoustic sensor 14 being physically connected to ancillary equipment. However, as noted above, with reference to Fig. 5A and Fig. 5B the vibroacoustic sensor components may be incorporated in a device similar to a smartwatch (see Fig. 5A) such that the user / patient can wear the vibroacoustic sensor over a prolonged period of time. Such a device can be programmed to allow measurements / data to be recorded over that period of time and accessed and analysed locally, remotely or downloaded at the next clinician visit. Similarly, in the example of a handheld device 110 as illustrated in Fig. 5B the device can be programmed to allow measurements / data from each use to be recorded to the device. Such data can then be accessed, for analysis locally, remotely or downloaded at the next clinician visit.

[0117] Adopting the components of the vibroacoustic sensor in such devices would allow remote management of the sensor and also allow remote assessment.

[0118] The vibroacoustic sensor 14 according to the examples described and illustrated, allows for continuous, regular or sporadic monitoring of changes in skin layer characteristics during healing of a wound or due to skin conditions such as eczema, psoriasis etc. A comparison of healthy and unhealthy skin condition due to eczema and psoriasis is illustrated in Fig. 6A. Fig.

[0119] 6B illustrates an example utility of the vibracoustic sensor 14 on skin affected by eczema. Continuous or point-of-care monitoring allows for data-driven intervention and to optimise treatment plans for each patient. This means that any wound or skin condition could potentially heal / improve at an enhanced rate due to the ability to tailor treatment and remove diagnostic uncertainty / bias. This has the benefit of reducing healthcare service costs and reducing clinic time for the patient and the clinician.

[0120] Fig. 7A and Fig. 7B represent blood flow characteristics of the skin layers as an example application of the vibracoustic sensor 14. In this example the vibroacoustic sensor 14 is applied to the skin 18 as discussed above with reference to Fig. 2B, 5A and 5B. However, in this example the data output from the sensor 14 is used to represent characteristics andchanges in blood flow in the skin layers. The sensor 14 may be used to detect systemic changes as well as local skin changes. For blood flow monitoring e.g., in respect of conditions such as peripheral artery disease, changes due to the quality of blood flow, diabetes related changes, microvascular changes, injuries, inflammatory skin diseases etc., in this example the output of the receivers is used to provide a graphical representation of blood flow as illustrated graphically in Fig. 7A and Fig. 7B. Fig. 7A represents blood flow changes in the epidermis, presented as viscosity and stiffness properties over time. Similarly, Fig. 7B represents blood flow changes in the epidermis, presented as viscosity and stiffness properties overtime. Essentially, Fig. 7Aand 7B illustrate an example application of the sensor described above and illustrated in Fig. 2B, 5A and 5B.

[0121] While the invention has been shown and described with reference to certain exemplary embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention as defined by the appended claims.

Claims

CLAIMS1. A non-invasive method of obtaining layer-specific properties of tissue layers comprising an outer layer and underlying layers, the method comprises:placing a vibroacoustic sensor in responsive contact with an outer surface of the outer layer of the tissue layers,activating the vibroacoustic sensor to create vibratory motion at the outer surface of the outer layer, thereby generating vibroacoustic waves through all layers;detecting the generated vibroacoustic waves with the vibroacoustic sensor thereby generating output data;generating a phase velocity dispersion curve using the output data;analysing discontinuities in the phase velocity dispersion curve with a mathematical model to obtain layer-specific properties of each tissue layer, wherein the discontinuities represent boundaries between tissue layers.

2. The method as claimed in claim 1, wherein the analysing step comprises applying the mathematical model consecutively to the discontinuities in the phase velocity dispersion curve to obtain layer-specific properties of each tissue layer, wherein the discontinuities represent frequency regions associated with each tissue.

3. The method of claim 2, wherein applying the mathematical model comprises applying a first mathematical model to the frequency region associated with the outer layer and obtaining layer specific properties of the outer layer and subsequently applying a further mathematical model to the frequency region associated with each underlying layer consecutively utilising data obtained from a previous layer in analysing each subsequent layer.

4. The method of claim 3, wherein the first mathematical model is a homogeneous shear wave mathematical model.

5. The method as claimed in claim 3, wherein surface-acoustic wave interpretation is used to supplement interpretation of the outer layer properties obtained from the homogeneous shear wave model.

6. The method as claimed in any of claims 3 to 5, wherein the first mathematical model determines shear elasticity and shear viscosity characteristics of the outer layer.

7. The method as claimed in any of claims 3 to 6, wherein the further mathematical model is a heterogeneous shear wave model.

8. The method as claimed in claim 7, wherein the heterogenous wave model is expressed by equation:wherein Cs(") isadata set of estimated wave velocities for a variety of tested frequencies, a> is the angular frequency, p is material density, n is a number associated with the tissue layer being analysed, wherein n = 2 is a first layer directly underlying the outer layer and n = 3, n= 4 etc. are underlying layers counted consecutively from the first underlying layer.

9. The method as claimed in claim 8, wherein the layer specific properties of each tissue layer is determinable when properties of an overlying layer is known, wherein the first underlying layer properties are determinable after determining the outer layer properties, a second underlying layer properties are determinable after determining the first underlying layer properties and so on until properties of all tissue layers are determined.

10. A vibroacoustic sensor configured to be placed or worn in responsive contact with tissue layers comprising an outer layer and underlying layers, wherein the vibroacousticsensor is operable to non-invasively actively monitor / measure properties of the outer layer and the underlying layers, the vibroacoustic sensor comprising:at least one vibratory source; andat least one receiver displaced relative to the at least one vibratory source, wherein the at least one vibratory source is operable to create vibratory motion to an outer surface of the outer layer, thereby generating vibroacoustic waves through all layers; andwherein the at least one receiver is operable to detect the vibroacoustic waves and provide collectable output data, which output data being configured for analysis to determine layer-specific properties of each tissue layer.

11. The vibroacoustic sensor as claimed in claim 10, wherein the at least one vibratory source is a piezoelectric transducer.

12. The vibroacoustic sensor as claimed in claim 10 or 11 , wherein the at least one receiver is a piezoelectric transducer.

13. The vibroacoustic sensor as claimed in any of claims 10 to 12, including two receivers per single associated vibratory source, wherein each receiver is spaced from the associated vibratory source and the receivers are also spaced from each other.

14. The vibroacoustic sensor as claimed in claim 13, wherein the receivers are each displaced about a longitudinal axis of the associated vibratory source and about a transverse axis of the associated vibratory source.

15. The vibroacoustic sensor as claimed in claim 14, wherein each receiver is displaced by between 1mm and 10mm relative to the longitudinal axis of the associated vibratory source and relative to the transverse axis of the associated vibratory source and relative to each other.

16. The vibroacoustic sensor as claimed in any of claims 10 to 15, wherein the at least one vibratory source provides local vibration to the outer surface of the outer tissue layer at a frequency between 0.1 to 20 kHz.

17. The vibroacoustic sensor as claimed in any of claims 10 to 16, comprising film layers supporting the at least one vibratory source and the at least one receiver.

18. The vibroacoustic sensor as claimed in as claimed in any of claims 10 to 17, further comprising conformable electrodes, wherein respective conformable electrodes are attached to each of the at least one vibratory source and the at least one receiver.

19. The vibroacoustic sensor as claimed in claim 18, wherein the conformable electrodes are sandwiched between two film layers.

20. The vibroacoustic sensor as claimed in any of claims 10 to 19, further comprising an adhesive layer operable to support and protect the vibratory source and receivers.

21. The vibroacoustic sensor as claimed in any of claims 10 to 20, further comprising encapsulation operable in use to encapsulate / house the at least one vibratory source and the at least one receiver.

22. The vibroacoustic sensor as claimed in claim 21, when dependent on claim 19, wherein the encapsulation is positioned above the film layers.

23. The vibroacoustic sensor as claimed in claim 17, wherein the film layers are made from flexible polymers.

24. The vibroacoustic sensor as claimed in any of claims 18 to 23, wherein the conformable electrodes are made from conductive material coated flexible polymers.

25. The vibroacoustic sensor as claimed in claim 24, wherein the conformable electrodes are made from metal coated PEI film.

Images