The present disclosure relates to the field of measurements of the mechanical properties of a human or animal skin sample.
More particularly, it relates to devices for measuring the mechanical properties of a skin sample ex vivo or in vitro, deposited and held fixed on a nutritional medium.
Skin has a complex multilayer structure, stratified with three main layers from the surface inwards: the epidermis, dermis and hypodermis. The structural complexity of the skin gives it mechanical properties: anisotropy, elastic behavior, viscoelastic behavior, heterogeneity. The skin can thus be seen as a complex material, the mechanical response of which depends on a large number of factors specific to the person and their living environment: age, sex, health, diet, environment, and region of the human body.
The study of the mechanical properties of the skin in response to a mechanical stress in vivo provides a certain amount of information of primary importance in many fields of cosmetics, surgery and medicine. It is thus known to measure the mechanical properties of the skin in order to evaluate, for example, the state of healthy skin or the changes induced by external products applied to a region of interest of the skin.
Among the mechanical stresses to which the skin is subjected in order to measure the mechanical properties, an important category of mechanical stresses to be applied are tensile stresses in the plane of the skin. The mechanical responses of the stressed skin are then measured by various sensors.
Currently, mechanical stress devices exist which enable traction to be exerted in the plane of the skin.
An example is the extensometer, which can carry out uniaxial traction tests in vivo, by attaching two pads on the skin and moving them in opposite directions. The pads are bonded on the skin in vivo. The bonding is performed with double-sided adhesive strips or with suitable glues.
However, this technique has some disadvantages. Specifically, the use of strong adhesives to obtain an effective anchoring point can, for example, damage the surface layer of the skin when the pads are removed. Hence, it is difficult to recommend this technique for performing tests carried out at the same location on the skin in vivo in order to evaluate the change in mechanical properties over time.
The adhesive strips are less invasive and better tolerated by the patient's skin. However, they do not allow sufficiently strong anchoring points to be obtained, thus giving rise to a risk of a displacement between the pad in contact with the skin and the measurement region, thus causing erroneous measurements.
Hence, current devices are not very accurate for monitoring the change in the mechanical behavior of a given region of the skin in vivo over time.
Another disadvantage is that, between two tests, spaced apart in time, in the event of monitoring over several days, for example, of the skin in vivo, the pads must be able to be removed between two tests and repositioned, which can induce inaccuracies in the location of the studied region which can impact on the reproducibility of the test results.
Another disadvantage is that current devices are mainly developed for mechanical characterization of the skin in vivo. However, once sampled, the skin loses its mechanical properties over time. Also, it is not currently possible to correctly evaluate the change in mechanical properties over time in a skin in vitro. However, in the case of mechanical characterization of the skin in vivo, the devices and methods must be non-invasive, which leads to limits in the study of the mechanical behavior. In the study of the non-linearity of the force-displacement relation, for example, it is not possible to study the phase corresponding to the rupture phase in the case of characterization of the skin in vivo.
The invention proposes to overcome these disadvantages.
Thus, it is sought to solve the problems posed by the prior art by developing a measuring device capable of evaluating the mechanical properties of the skin ex vivo, which is accurate, cost-effective and easy to use.
Another aim of the invention is to provide a measuring device capable of carrying out measurements in various possible directions in the plane of the skin.
Another aim of the invention is to provide a measuring device capable of producing mechanical traction stresses parallel to the surface of the skin ex vivo, the mechanical properties of which are maintained over time, and of performing reproducible measurements of the mechanical properties.
For this purpose, the object of the present disclosure is a system for measuring the mechanical properties of a skin sample ex vivo or in vitro, comprising a measuring device comprising at least one mechanical stress module capable of applying a tensile force to the skin in a direction parallel to the surface of the skin sample, said at least one mechanical stress module comprising:
According to one embodiment of the invention, a plurality of mechanical stress modules are arranged around a center of the device and configured to each apply a tensile force in a radial direction parallel to the surface of the skin sample, and the axial displacement means and the translating arms are aligned in pairs so as to displace two traction means along a common displacement axis.
According to one embodiment of the invention, the aligned axial displacement means are synchronized so as to simultaneously displace two traction means along the common axis.
According to one embodiment of the invention, the axial displacement means comprises a piezoelectric nano-positioning table, one end of the translating arm being attached on a moving part of the piezoelectric nano-positioning table.
According to one embodiment of the invention, each stress module further comprises a manual micrometric displacement table configured to manually adjust the position of the translating arm along one of the axes of displacement.
The piezoelectric nano-positioning table and the micrometric displacement table are preferably arranged with respect to one another so as to have the same axis of displacement.
The features disclosed in the following paragraphs can, optionally, be implemented independently of one another or in combination with one another:
The attachment head is in the form of a rod provided with a thread capable of engaging in the thickness of the skin sample to produce a point of attachment in the skin sample.
The attachment head is in the form of a straight cylindrical body, one of the bases of the straight cylindrical body being provided with a layer of adhesive to attach the attachment head to the surface of the skin sample.
The traction means comprises a cylindrical attachment body intended to be received in a recess produced in one end of the translating arm and locked in position using a clamping element.
According to one exemplary embodiment of the invention, the measuring device further comprises at least one tensile force sensor capable of measuring the tensile force applied by a traction means.
According to another exemplary embodiment of the invention, the measuring device further comprises at least one position measurement sensor capable of measuring the position of a translating arm during its displacement.
According to another exemplary embodiment of the invention, the measuring device further comprises at least one imaging means configured to observe the region of deformation of the skin sample caused by the displacement of the attachment heads, the optical axis of said imaging means being oriented in a direction normal to the surface of the skin sample.
Further features, details and advantages will emerge from reading the following detailed description and analyzing the appended drawings, in which:
In the context of the present disclosure, “mechanical properties” means the physical parameters which can be defined from the deformation of the skin subject to a mechanical stress. Indeed, by analyzing the mechanical responses to the imposed deformation, it is possible to demonstrate the elastic, viscoelastic and plastic properties of the skin.
When traction is exerted on the skin, there is an extension of the skin due to the dermal elastic networks. When the force ceases, the skin retracts with an elastic return to its initial state. In the case of large extension, the deformation is plastic and irreversible.
In the context of the present disclosure, “ex vivo skin sample” means a skin sample taken from a living body and which is kept alive by a nutritional solution, throughout the entire duration of the measurement of the mechanical properties. Consequently, the ex vivo skin sample normally functions as in vivo skin for a determined duration.
In the context of the present invention, “in vitro skin sample” means a synthetic skin sample produced in the laboratory. However, the studies on in vitro skin cannot be used to characterize the natural functioning of skin which is still living.
The device of the present disclosure can be used on any type of skin sample. The device of the present disclosure was designed, in particular, for the purpose of characterizing mechanical properties of a skin sample ex vivo held in a fixed position on a nutritional medium which enables the mechanical properties of the skin sample to be maintained for a duration of at least seven days. The technique of keeping an ex vivo skin sample alive is described in document WO2013164436.
The measuring device of
According to one embodiment of the invention, the mechanical stress modules function as pairs. In
The four mechanical stress modules 20, 40, 70 and 80 are supported by a frame 100 intended to be placed and stabilized on a horizontal surface of a table, for example. The frame comprises a base 103 forming a substantially horizontal surface which extends in a horizontal plane (XY). The center of the base 103 is provided with a substantially circular opening 104. The two axes (AA′) and (BB′) are secants at a point located substantially at the center of the opening. The base 103 also comprises a passage 105 which extends from the central opening 104 to an edge of the base.
The measuring device 10 comprises a sample holder 5, visible in
With reference to
The mechanical stress modules are described in more detail below, with reference to
The first mechanical stress module 20 comprises a first translating arm 21 connected on the one hand to a first traction means 30 and on the other hand to a first displacement means 24. The first traction means 30 comprises an attachment head 31 (visible in
The second mechanical stress module 40 comprises a second translating arm 41 connected on the one hand to a second traction means 50 and on the other hand to a second displacement means 44. The second traction means 50 comprises an attachment head 51 (visible in
The third module 70 and the fourth module 80 are structurally identical to the second module 40 and the first module 20, respectively. Their respective traction means can likewise induce a deformation of the sample by axially displacing two other points of attachment of the sample along the axis (AA′).
The function of the two modules 20, 40 is to exert an opposing tensile force along a common axis (BB′). The function of the two modules 70, 80 is to exert an opposing tensile force along a common axis (AA′).
In the exemplary embodiment illustrated in
According to one embodiment, the displacement means comprises a piezoelectric nano-positioning table 24, 44, 74, 84. One end of the translating arm 21, 41, 71, 81 is attached on a moving part of the piezoelectric nano-positioning table in order to displace the traction means. The piezoelectric nano-positioning table can control the deformation of the sample by axially displacing the translating arm. In order to exert an opposing tensile force along a common axis, the piezoelectric nano-positioning tables of the aligned mechanical stress modules are likewise aligned in pairs with respect to one another so as to have the same axis of displacement. The piezoelectric nano-positioning table 24 associated with module 20 and the piezoelectric nano-positioning table 44 associated with module 40 have the same axis of displacement (BB′). The piezoelectric nano-positioning table 74 associated with module 70 and the piezoelectric nano-positioning table 84 associated with module 80 have the same axis of displacement (AA′).
According to one embodiment of the invention of the present disclosure, the aligned piezoelectric displacement tables are synchronized so that the displacements of the traction means are synchronized. In this configuration, the tensile force exerted by the opposite displacements of the aligned piezoelectric tables has the same value at any point on the axis of displacement. Thus, a single tensile force sensor is necessary for measuring the tensile force per axis of displacement between the two aligned piezoelectric nano-positioning tables.
According to an advantageous embodiment of the present disclosure, the measuring device comprises a single tensile force sensor 22, 82 per pair of aligned mechanical stress modules, in other words per axis of displacement. In the exemplary embodiment illustrated in
The measuring device further comprises one position measurement sensor 27, 87 per pair of aligned mechanical stress modules, in other words per axis of displacement. In the exemplary embodiment illustrated in
According to one embodiment of the invention, and with reference to
The traction means 30, 50, carried respectively by the aligned modules 20, 40, is described below, with reference to
The traction means 30, 50 comprises a main axis Z1, Z2 oriented in a vertical direction substantially normal to the surface of the skin. The traction means 30, 50 comprises a substantially cylindrical body 34, 54, being provided at one end with an attachment head 31, 51, intended to be attached to the skin 3 during operation of the measuring device 10.
The traction means 30, 50 is attached by mechanical attachment means to the tip 23, 43 of the translating arm 21, 41. A recess 28, 48 is produced in the tip 23, 43. The cylindrical body 34, 54 of the traction means 30, 50 is received in the recess 28, 48 and locked in position using a clamping element 29, 49. The traction means 30, 50 further comprises an annular support surface 32, 52 located at the end of the cylindrical body which is provided with the attachment head. This support surface 32, 52 is capable of abutting against the periphery of the recess 28, 48 when the cylindrical body 34, 54 of the traction means 30, 50 is inserted in the recess. The traction means 30, 50 is removably and interchangeably mounted with respect to the translating arm 21, 41. As illustrated in
In the case where this form of attachment head is used, when the test is ended, the operator lowers the sample holder 5 in the vertical direction in order to take the attachment head out of the skin and displaces the sample holder in a direction parallel to the skin on the rail 61 (
According to a second embodiment (B), the attachment head 91 is in the form of a substantially cylindrical body 93, the base 95 of which is provided with a layer of adhesive allowing attachment of the attachment head to the surface of the skin. This layer of adhesive can, for example, be a layer of epoxy or any other adhesive suitable for attaching the attachment head to the surface of the skin. In the case where this second embodiment of the attachment head is used in order to obtain a point of attachment on the skin sample, when the traction test is ended, it is necessary to extract the traction means 30, 50 from its recess 28, 48 by unscrewing the clamping screws 29, 49. The traction means 30, 50 are then removed from the measurement region, in other words the center of the base with the attachment heads glued to the surface of the skin sample.
According to one embodiment of the invention, the measuring device also comprises an imaging means 110 configured to observe and record the region of deformation of the surface of the skin caused by the displacement of the attachment heads. By way of example, the imaging means 110 can be a color camera positioned above the surface skin with the optical axis (Z3) oriented in a direction normal to the skin surface, with adjustable magnification, but can also be a more precise microscopy device.
The position sensors 27, 87 illustrated in
The system 200 also comprises other means which enable the skin sample to be characterized, for example a radiation scattering system, an ellipsometer or an epi-fluorescence microscope.
The control unit 202 comprises a control program which controls the displacement means 24, 44, 74, 84 of the measuring device 10 in order to displace the translating arms, which displace the corresponding attachment head in translation in the plane of the skin sample.
The tensile force sensors 22, 42, the position measurement sensors 27, 47 and the imaging means 110 are connected to the control unit 202.
According to one embodiment, the control unit is configured to control the displacement means at a stress frequency of between 0.1 mHz and 1 Hz. The shape of the stress frequency can be sinusoidal, triangular or rectangular. More precisely, the control unit 202 is configured to control the displacement of the translating arm in a sinusoidal, triangular or rectangular manner, by varying various parameters such as the stress frequency and the deformation of the sample. The stress frequency can vary between 0.1 mHz and 1 Hz, preferably between 0.1 Hz and 1 Hz and the deformation of the sample can vary between 0.001% and 10%.
The calculation unit 203 is configured to receive signals transmitted by the sensors of the measuring device. The set of signals measured by the sensors of the measuring device is then processed by the calculation unit 203 in order to calculate the mechanical properties of the skin, in particular to track the stress as a function of the deformation.
Controlling the displacement arm in a precise frequency range makes it possible to measure mechanical properties of the skin for large stress times, thus highlighting the effects of viscoelasticity in order to characterize the overall behavior of the skin. Contrary to the stresses at controlled speed for mechanical analysis of a biological tissue usually proposed in the methods of the prior art, the inventors propose a measuring system based on a stress over a range of frequencies, thus making it possible, in a single measurement phase, to determine the evolution of the complex modulus of the skin as a function of various stress frequencies. The measurement of the complex modulus as a function of the stress frequency enables a breakdown into two values: the real part, in phase with the stress signal, which can characterize the elastic properties of the skin and the imaginary part, which can characterize the dissipation properties of the skin.
The device 10 of the present disclosure has been designed to enable measuring of the mechanical properties of a human skin sample, ex vivo or in vitro, as a function of a plurality of parameters. The device can impose a deformation on the sample and measure the stress resulting from this deformation. The mechanical stresses are produced with tractions in various directions in the plane of the skin and with various frequencies. Hence, the stress-deformation curves obtained by the device at various frequencies enable elastic, plastic and viscoelastic properties of the skin subjected to a stress to be probed.
Performing the measurements on an ex vivo sample advantageously makes it possible to study the mechanical properties in the region beyond the elastic properties, also referred to as the non-linear region, by subjecting the skin sample to a high deformation.
The device of the present disclosure is particularly suitable for monitoring the evolution over time of the mechanical properties of an ex vivo skin sample, held fixed on a nutritional medium for a duration of several days, and for establishing a link with the potential changes in the mechanical properties of the skin or the structure of the skin induced by an external product. Indeed, holding the skin ex vivo on a nutritional medium enables the skin to keep its mechanical properties as described in document WO2013164436, in contrast to a sample in vitro.
The device makes it possible to continuously monitor, with time over several days, the deformation of the skin and the return of the skin to its equilibrium state, while holding in position attachment points on the same region of the skin throughout the duration of the test, making it possible to obtain precise and reproducible measurements of the mechanical properties of the skin.
The device of the present disclosure can have application in the field of cosmetics and medicine, and any field which treats the human skin.
The device can, for example, based on measurements of mechanical properties, evaluate the changes to healthy skin over time due to the effect of cosmetic products such as moisturizing creams, sun-protection creams or anti-aging creams.
In the medical field, measurements of the mechanical properties make it possible, for example, to monitor the effects of products applied to promote healing or to treat a damaged area. It is also possible to monitor the evolution of the mechanical behavior of an area of the skin damaged by various actions, such as confinement under a dressing or pressure sores under the effect of friction.
The device can also monitor the evolution of the mechanical properties of the skin faced with environmental attacks, such environmental pollution or attack by the sun's rays.
Number | Date | Country | Kind |
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FR2013764 | Dec 2020 | FR | national |
Filing Document | Filing Date | Country | Kind |
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PCT/FR2021/052389 | 12/17/2021 | WO |