Bioimpedance measurement device

Abstract

Bioimpedance Measurement Device This description relates to a method for manufacturing a bioimpedance measurement device, comprising the following steps: - Providing a flexible substrate (100) comprising a polymer material (110) and electrically conductive lines (120), - Forming electrodes (200), preferably four electrodes, on the flexible substrate (100), the electrodes (200) being electrically connected to the conductive lines (120), the electrodes (200) being formed by printing, photolithography, or transfer of an electrically conductive adhesive material. Figure for the abstract: Fig. 1

Description

Title of the invention: Bioimpedance measuring device Technical field

[0001] The present description relates generally to the field of flexible (conformable) medical devices worn on the person for bioimpedance measurements, and in particular for determining the hydration level of a subject. Prior art

[0002] Bioimpedance measurements are used to determine the electrical characteristics of living tissues. Bioimpedance is used, for example, to analyze tissue composition or to monitor time-dependent biosignals, such as signals related to respiration, the cardiovascular system or muscle contractions.

[0003] To determine an individual's hydration level, bioimpedance measurements are performed on the skin. The skin comprises several layers: the stratum corneum on the surface, the epidermis, the dermis and the hypodermis. The dermis is the target tissue to study since it is considered one of the water reservoirs of the human body. The dermis is said to contain up to 2.7 L of water and its water volume would be impacted during an episode of dehydration.

[0004] Generally, the measurement of the hydration rate consists of applying an alternating current of a few mA by means of a first pair of electrodes on the skin. Simultaneously, a second pair of electrodes, also positioned on the skin, measures the voltage. The ratio between the measured voltage and the applied current gives a complex impedance value containing both magnitude and phase values.

[0005] One of the main problems with this type of measurement is that the impedance values ​​obtained depend on several factors, in particular the position of the electrodes and / or the spacing between electrodes, the humidity or hairiness of the skin, but also the thickness of the different layers forming the skin (dermis, epidermis).

[0006] Furthermore, it is difficult to represent the skin-electrode interface by a simple series connection of the electrode impedance and the skin impedance, since the electrode and the skin influence each other during the measurement.

[0007] Furthermore, the electrical stability of the measurement is essentially based on the quality of contact between the skin and the electrode. However, this interface comprises four different conductive layers: - the first layer represents the electrode itself, which has a resistive behavior (depending in particular on the materials used), - the second layer is the actual interface between the electrode and the skin (capacitance of contact), - the third layer represents the stratum corneum and the epidermis and can be represented by a parallel connection of a resistance and a capacity, - the fourth and last layer is the dermis having a resistive electrical behavior.

[0008] Due to various parameters, and in particular the electrode-skin interface which may include air inclusions or other elements causing additional capacitive behavior, it may be difficult to have a reliable and reproducible measurement. Summary of the invention

[0009] There is therefore a need to obtain a device or method for measuring the bioimpedance of a subject reliably, the device used having to be flexible (conformable) in order to increase the comfort of the subject (typically patient).

[0010] This aim is achieved by a method of manufacturing a bioimpedance measuring device comprising the following steps: - Provide a flexible substrate comprising a polymer material and electrically conductive lines, - Forming electrodes, preferably four electrodes, on the flexible substrate, the electrodes being electrically connected to the conductive lines, the electrodes being formed by printing, by photolithography or by transfer of an electrically conductive adhesive material.

[0011] Advantageously, the electrically conductive lines are made of silver, preferably printed silver, or gold.

[0012] Advantageously, the transfer of the electrically conductive adhesive material is carried out by means of a transparent transfer layer.

[0013] Advantageously, the electrodes are formed by transferring an element to be transferred in an electrically conductive adhesive material, comprising a first part having the shape of the electrodes and a second part intended to serve as a support during the transfer.

[0014] Advantageously, the transfer of the electrically conductive adhesive material is carried out according to the following sub-steps: - pre-cut the element to be transferred from a film of electrically conductive adhesive material, - position the element to be transferred on the transparent transfer layer, preferably made of a fluoropolymer, - glue the first part in the shape of the electrodes onto the flexible substrate, - separate the first part having the shape of the electrodes from the second part and the transparent transfer layer, whereby the electrodes are transferred to the flexible substrate.

[0015] This aim is also achieved by a bioimpedance measurement device comprising: - a flexible substrate comprising a polymer material and electrically conductive lines, - electrodes, preferably four electrodes, arranged on the flexible substrate, the electrodes being electrically connected to the conductive lines, the electrodes being made of an electrically conductive adhesive material, a printed electrically conductive material or an electrically conductive material deposited by photolithography.

[0016] Advantageously, the electrically conductive lines are made of printed silver.

[0017] Advantageously, the polymer material is thermoplastic polyurethane, polyimide, silicone, polyethylene terephthalate or polyamide.

[0018] According to a first advantageous variant, the electrodes made of a printed electrically conductive material are Ag / AgCl electrodes.

[0019] According to a second advantageous variant, the electrodes made of an electrically conductive adhesive material are made of a composite material comprising a polymer chosen from (meth)acrylates, polysiloxanes and their mixtures and an electrically conductive element, preferably particles, for example carbon particles, and / or an electrically conductive polymer, for example polyaniline or poly (3,4-ethylenedioxy thiophene).

[0020] This aim is also achieved by a method for measuring the bioimpedance of a subject comprising the following steps: - positioning, on the skin of a subject, a device comprising a flexible substrate and four electrodes arranged on the flexible substrate, the flexible substrate comprising a polymer material and electrically conductive lines, the four electrodes being electrically connected to the electrically conductive lines, the four electrodes comprising two distal electrodes and two proximal electrodes, the electrodes being made of an electrically conductive adhesive material, a printed electrically conductive material or a material deposited by photolithography, - apply a current between the two distal electrodes, - measure the voltage between the two proximal electrodes, - calculate the impedance from the applied current and the measured voltage and determine, for example, the subject's hydration rate.

[0021] Advantageously, the electrodes are made of a composite material comprising a polymer chosen from (meth)acrylates, polysiloxanes and their mixtures and an electrically conductive element, preferably particles, for example carbon particles, and / or an electrically conductive polymer, for example polyaniline or poly(3,4-ethylenedioxythiophene). Brief description of the drawings

[0022] These characteristics and advantages, as well as others, will be explained in detail in the following description of particular embodiments given without limitation in relation to the attached figures among which:

[0023] [Fig.l] represents, schematically and in section, a device for measuring bioimpedance according to a particular embodiment of the invention;

[0024] [Fig.2] represents, schematically and in section, a device for measuring bioimpedance according to another particular embodiment of the invention;

[0025] [Fig. 3] represents, schematically and in section, a device for measuring bioimpedance according to another particular embodiment of the invention;

[0026] [Fig.4] is a photographic image representing particular arrangements of electrodes according to different embodiments of the invention;

[0027] [Fig.5A], [Fig.5B], [Fig.5C] and [Fig.5D] are photographic images representing different steps for transferring electrodes to a substrate according to a particular embodiment of the invention;

[0028] [Fig.6A], [Fig.6B], [Fig.6C] and [Fig.6D] are photographic images representing devices for measuring bioimpedance according to different particular embodiments of the invention;

[0029] [Fig.7] is a photographic image representing a substrate on which electrodes and various electronic elements are arranged, according to a particular embodiment of the invention;

[0030] [Fig.8A] and [Fig.8B] are photographic images representing different devices for measuring bioimpedance, each comprising an adhesive film for holding the device on a subject, according to different particular embodiments of the invention;

[0031] [Fig.9] represents, schematically and in section, a device for measuring bioimpedance, according to another particular embodiment;

[0032] [Fig. 10] is a photographic image of a device for measuring bioimpedance, according to another particular embodiment, the dotted lines delimit an area covered by an adhesive layer;

[0033] [Fig. 1 1] is a schematic and sectional representation of a device for measuring bioimpedance according to another particular embodiment of the invention;

[0034] [Fig.l2A] and [Fig.l2B] are photographic images representing different devices for measuring bioimpedance according to different particular embodiments of the invention;

[0035] [Fig.13], [Fig.14] and [Fig.15] are schematic and sectional representations of different devices for measuring bioimpedance according to different particular embodiments of the invention;

[0036] [Fig. 16] is a photographic image of a device for measuring bioimpedance, comprising an adhesive film for holding the device on a subject and an absorbent element, according to a particular embodiment of the invention. Description of the embodiments

[0037] The same elements have been designated by the same references in the different figures. In particular, the structural and / or functional elements common to the different embodiments may have the same references and may have identical structural, dimensional and material properties.

[0038] For the sake of clarity, only the steps and elements useful for understanding the described embodiments have been shown and are detailed.

[0039] Unless otherwise specified, when referring to two elements connected to each other, this means directly connected without intermediate elements other than conductors, and when referring to two elements connected (in English "coupled") to each other, this means that these two elements can be connected or be connected by means of one or more other elements.

[0040] In the following description, when reference is made to absolute position qualifiers, such as the terms "front", "back", "top", "bottom", "left", "right", etc., or relative position qualifiers, such as the terms "above", "below", "upper", "lower", etc., or to orientation qualifiers, such as the terms "horizontal", "vertical", etc., reference is made unless otherwise specified to the orientation of the figures.

[0041] Unless otherwise specified, the expressions "about", "approximately", "substantially", and "of the order of" mean to within 10%, preferably to within 5%.

[0042] We will now describe the device in more detail with reference to the attached figures.

[0043] The device can be produced according to one of the following embodiment variants or a combination of these variants.

[0044] The bioimpedance measurement device comprises at least one flexible substrate 100 (conformable for patient comfort and / or to improve electrode / skin contact) on which electrodes 200 are arranged.

[0045] According to a first variant embodiment, notably shown in FIGS. 1, 2, 3, 4, 5A to 5D, 6A to 6D, 7, 8A and 8B, the flexible substrate 100 comprises a polymer material 110 and electrically conductive lines 120, the electrodes 200 being electrically connected to the conductive lines 120.

[0046] The electrodes 200 may be made of a printed electrically conductive material, obtained by printing an ink or a paste, in an electrically conductive material deposited by photolithography or in an electrically conductive adhesive material, obtained by transferring an electrically conductive adhesive element.

[0047] Such so-called dry electrodes 200 are more comfortable for the subject. Dry electrodes do not require the use of a gel in liquid form during the measurement, as is the case during ultrasound sessions. The quality of the electrical signal is improved compared to such electrodes. The dry electrodes may contain a crosslinkable dry electrolyte. The gel / hydrogel is here permanent and forms an integral part of the electrode. For example, a crosslinkable mixture comprising a crosslinkable polysiloxane (silicone), an electrolyte and a conductive element, such as a carbon wire / fiber type conductor or carbon particles, may be used.

[0048] These electrodes 200 can be easily miniaturized. With such electrodes 200, the electrode-skin impedance is thus reduced compared to so-called wet electrodes which contain a gel-type electrolyte or a hydrogel.

[0049] Advantageously, the risks of measurement error are, generally speaking, much lower compared to wet electrodes for which the gel tends to dry out during the measurement, which reduces the reproducibility of the measurement over time. The signal is much more stable and of better quality for dry electrodes.

[0050] Such electrodes have low roughness and are conformable (i.e. their shape adapts well, for example, to the subject's skin).

[0051] Dry electrodes also reduce the risk of allergies compared to wet electrodes.

[0052] The different materials will be described in more detail later.

[0053] According to a second alternative embodiment, notably shown in FIGS. 9, 10, 11, 12A and 12B, the flexible substrate 100 is covered by electrodes 200 and by adhesive zones 500, the adhesive zones 500 being arranged between the electrodes 200. The adhesive zones 500 are intended to be in contact with the skin 400 and make it possible to improve the hold of the device on the subject. Such a device can last for a period of at least 7 days. The adhesive zones 500 may comprise cavities or through holes 510 for containing fluids, such as bodily fluids, in particular sweat.

[0054] Such a device is particularly interesting since it has good mechanical strength on the subject, thus promoting the obtaining of reliable and reproducible measurements, particularly over time.

[0055] According to a third variant embodiment, for example shown in Figures 13, 14, 15 and 16, the device is a dressing. It allows to come and press and apply on the electrodes in order to improve skin / electrode contact. The device comprises a flexible substrate 100, one of whose faces is covered by electrodes 200 and the other of its faces is covered successively by an absorbent element 700 and by an adhesive film 600. The substrate 100 further comprises through holes 510, arranged between the electrodes 200. The walls of the through holes are, advantageously, hydrophilic, so as to allow the evacuation of bodily fluid from the skin of the subject to the absorbent element 700. The absorbent element 700 is intended to absorb bodily fluids present on the subject, in particular sweat. The absorbent element 700 can penetrate into the holes 510 and thus facilitate the evacuation of sweat. Preferably, adhesive areas 500 cover the substrate 100, the adhesive areas 500 being positioned between the electrodes 200, the holes 510 pass through both the substrate 100 and the adhesive areas 500.

[0056] Such a device is particularly interesting since it makes it possible to manage bodily fluids and thus obtain reliable and reproducible measurements.

[0057] We will now describe in more detail these different embodiment variants which can be combined with each other.

[0058] The electrodes 200 are arranged on the flexible substrate 100.

[0059] The flexible substrate 100 is a conformable support, that is to say that it adapts to the reliefs of the surface on which it is placed.

[0060] The flexible substrate 100 comprises a first main face and a second main face.

[0061] According to the first embodiment, the flexible substrate 100 comprises a support made of a polymer material 110 and electrically conductive lines 120 positioned at the level of the first main face.

[0062] The polymer material 110 is, for example, thermoplastic polyurethane (TPU), polyimide (PI), silicone (polysiloxane), polyethylene terephthalate (PET) or polyamide (PA).

[0063] The polymer material 110 forms a support for the electrically conductive lines 120.

[0064] The electrically conductive lines 120 (also called electrically conductive tracks) are intended to be connected to the electrodes 200. The electrically conductive lines 120 and the electrodes 200 are positioned on the first main face of the substrate. The electrically conductive lines 120 are intended to be connected to one or more electrical devices making it possible to impose a current and to measure a voltage.

[0065] The electrically conductive lines 120 locally cover the polymer material 110. Their thickness is thick enough to conduct the electrical charges while being thin enough not to break when the substrate adapts to the relief on which it is positioned. For example, they may have a thickness of between 50 nm and 30 pm, preferably between 2 pm and 30 pm, in particular approximately 15 pm, in particular for printed electrically conductive lines 120. The electrically conductive lines 120 deposited by vacuum deposition (for example in gold) may have a thickness of between 50 nm and 1 pm, preferably between 100 and 250 nm, for example 150 nm.

[0066] At least a portion of the lines 120, or even all of the lines 120, are on the surface of the polymer material 110 so that they can be connected to the electrodes 200.

[0067] The electrically conductive lines 120 are preferably made of metal. For example, they are made of gold or silver.

[0068] The electrically conductive lines may be made of an electrically conductive polymer such as PEDOT-PSS.

[0069] According to an alternative, the electrically conductive lines 120 are made of a composite material comprising, for example, a non-electrically conductive polymer (for example polysiloxane (silicone) or thermoplastic polyurethane (TPU)) and an electrically conductive element, in particular in the form of fibers, threads or particles (for example carbon fibers or silver particles) and / or an electrically conductive polymer. Such lines are stretchable.

[0070] By way of illustration and non-limiting example, the electrically conductive lines 120 are for example made of gold 50 nm thick, PEDOT-PSS 2 pm thick, printed silver 1 to 30 pm thick.

[0071] The electrically conductive lines 120 can be deposited by any printing technique, in particular by screen printing. This embodiment is particularly advantageous in the case of silver lines.

[0072] Preferably, the electrically conductive lines 120 are obtained by depositing a silver paste. The silver paste is, for example, the paste marketed under the reference PE874 by the company DuPont™.

[0073] The gold lines 120 may be, for example, formed by photolithography. According to this particular embodiment, the lines and the electrodes may form a single element. According to this embodiment, the substrate 100 is preferably made of PI.

[0074] Preferably, the electrically conductive lines 120 are made of silver and the polymer material 110 is made of thermoplastic polyurethane.

[0075] Electrodes 200 are arranged on the flexible substrate 100. The electrodes 200 are electrically connected to the conductive lines 120.

[0076] The device preferably comprises an even number of electrodes 200. In particular, the device comprises two or four electrodes.

[0077] The electrodes 200 are intended to be coupled with the skin. Preferably, they are intended to be in direct contact with the skin. They make it possible to transmit an electrical signal to the subject's skin or receive an electrical signal from the subject's skin.

[0078] The electrodes furthest from the center are called distal and the electrodes closest to the center are called proximal.

[0079] In particular, the distal electrodes are used to impose a current and the proximal electrodes are used to measure the voltage resulting from the current imposed on the subject.

[0080] As shown in [Fig. 4], the electrodes 200 may be of different shapes. They are, for example, racetrack-shaped, circular or they may be in the form of lines. The electrodes 200 are preferably arranged concentrically in the case of circular electrodes or in the case of racetrack-shaped electrodes. In the case of linear electrodes, the electrodes are arranged in parallel.

[0081] The electrodes 200 may be spaced apart by a distance of between 1 and 2 mm, preferably between 1 and 1.5 mm. The width of the electrodes is, for example, between 1 and 2 mm, preferably between 1 and 1.5 mm.

[0082] The electrodes 200 may be formed by photolithography, by printing an ink or paste, or by transferring an electrically conductive adhesive material.

[0083] According to a first embodiment, the electrodes 200 are deposited by photolithography. The electrodes 200 may be made of gold.

[0084] According to a second embodiment, the electrodes 200 are made of a printed electrically conductive material. Such electrodes 200 are obtained by printing an ink or a paste.

[0085] The ink or paste may contain a solvent and possibly a binder. After depositing the ink or paste, the solvent is evaporated so as to obtain a dry binder if necessary.

[0086] The annealing temperature will be chosen according to the solvent. Typically, annealing at 120°C for 30 minutes will evaporate most of the solvents used with this type of electrode.

[0087] For example, the printed electrodes 200 are Ag / AgCl electrodes. Such electrodes comprise a layer of silver and silver chloride (to obtain an Ag-AgCl electrode). A carbon layer may be disposed between the flexible substrate and the Ag / AgCl layer, and, more particularly, between the electrically conductive track 120 and the silver layer.

[0088] For example, the Ag / AgCl layer can be deposited from the paste referenced 5880 and marketed by the company DuPont™. The carbon layer can be obtained from the paste referenced PE671 and marketed by the company DuPont™.

[0089] Alternatively, the printed electrodes 200 are made of a composite material comprising a polymer (for example a polyester or a polysiloxane (silicone), or one of their copolymers) or a resin and electrically conductive particles. For example, these can be silver and silver chloride particles, carbon, graphite. It is possible to choose an electrolytic material to match the skin / electrode impedances.

[0090] It is possible to print electrodes with a dry ink comprising, for example, carbon fibers, a silicone matrix and hydrogel. This allows for good conduction and good impedance matching with the skin.

[0091] According to a third embodiment, the electrodes 200 are made of an electrically conductive adhesive material. Such electrodes 200 are, for example, made of a composite material comprising a polymer and an electrically conductive element. The polymer may be chosen from (meth)acrylates, polysiloxanes and their mixtures (i.e. one of their copolymers). The electrically conductive element may be formed of fibers, wires or particles (for example carbon fibers or silver particles) and / or an electrically conductive polymer, for example polyaniline (PANI) or poly(3,4-ethylenedioxythiophene) (also noted PEDOT). The electrodes 200 may be lightly impregnated with electrolyte.

[0092] For example, it may be the material marketed under the reference Omni-Wave ™ TT 200 Black H-502 by the company Flexcon or it may be a material marketed under one of the references DuploMED® 22260, DuploMED® 45150 by the company Lohmann.

[0093] Such electrodes 200 can be obtained by transferring an element 220 comprising the preformed electrodes 200 onto the flexible substrate 100.

[0094] The element to be transferred 220 made of electrically conductive adhesive material advantageously comprises a first part having the shape of the electrodes 200 and a second part 210 intended to serve as a support during transfer. The first part and the second part are integral.

[0095] The holding element is, advantageously, made of the same material as the electrodes. The element to be transferred 220 is, for example, obtained by cutting an electrically conductive adhesive film 250.

[0096] For example, the transfer can be carried out by means of a transparent transfer layer 270, preferably made of a fluoropolymer. The method can be carried out according to the following sub-steps (FIGS. 5A to 5E): - pre-cutting an element to be transferred 220 in electrically conductive adhesive material from a film of electrically conductive material 250 ([Fig.5A]), - positioning the element to be transferred 220 on a transparent transfer layer 270 ([Fig.5B]), - gluing the first part having the shape of the electrodes 200 onto the flexible substrate 100, so as to connect the electrodes 200 with the electrically connected lines conductive 120 of the flexible substrate; advantageously, the second part 210 of the element to be transferred 220 is not glued to the flexible substrate 100 ([Fig.5C]), - remove the holding element 210 and the transparent transfer layer 270 ([Fig.5D])•

[0097] Alternatively, the element to be transferred 220 may be initially positioned between two transparent non-adhesive layers ('liner'). One of the layers is then removed at the first portion 200. The second portion 210 preferably remains positioned between the two transparent non-adhesive layers. The element to be transferred 220 is then positioned on the flexible substrate 100. The use of transparent non-adhesive layers facilitates the positioning of the electrodes 200 on the electrically conductive lines 120.

[0098] The electrodes 200 are thus transferred onto the flexible substrate. The second part can then be cut out.

[0099] The reporting step can be performed manually or automatically.

[0100] By way of illustration and not limitation, the substrate 100 and the electrodes 200 may correspond to the following elements: - a flexible substrate 100 comprising a polymer material 110, for example TPU, and electrically conductive lines 120 made of silver, covered by Ag / AgCl electrodes 200 (the electrodes 200 being able to be, for example, in the form of a bilayer comprising a carbon layer and an Ag / AgCl layer), which can be covered by a hydrogel, for example the hydrogel marketed under the reference DuroTak 9264 from the company Henkel ([Fig.6A]), - a flexible substrate 100 comprising a polymer material 110, for example PI, and electrically conductive lines 120 made of gold acting as electrodes 200, preferably covered by a layer of hydrogel 300, for example the hydrogel marketed under the reference DuroTak 9264 from the company Henkel ([Fig.6B]), - a flexible substrate 100 comprising a polymer material 110, for example TPU, and electrically conductive lines 120 made of silver, covered by electrodes 200 made of an electrically conductive adhesive material, obtained for example by transferring a preformed electrically conductive adhesive in the form of electrodes, for example the adhesive marketed under the reference Flexcon H-502 ([Fig.6C]), - a flexible substrate 100 comprising a polymer material 110, for example TPU, and electrically conductive lines 120 made of silver, covered by dry electrodes 200, obtained for example by depositing an ink comprising, for example, carbon fibers, a silicone matrix and hydrogel. This allows for good conduction and good impedance matching with the skin ([Fig.6D]).

[0101] A dielectric layer may be positioned on the electrodes 200 to protect them, in particular on the Ag / AgCl electrodes.

[0102] According to a particular embodiment, the electrodes can be covered with an adhesive, in particular an ionically conductive adhesive, to improve the contact between the skin and the electrodes. The adhesive will be chosen so as to be compatible with the measurement to be carried out (for example compatible with an ECG application). This embodiment is particularly advantageous in the case where the electrodes have a rough surface and / or if the skin / electrode contact is not sufficient. The ionically conductive adhesive makes it possible to adapt the impedance. It also makes it possible to prevent the aging of the electrodes. The electrical and mechanical stability is thus improved. The adhesive power of the adhesive areas is greater than that of a gel.

[0103] The adhesive is for example an acrylate, an acrylate-vinyl-acetate or one of their copolymers. For example, it is possible to choose an adhesive marketed under the reference Durotak by the company Henkel or the adhesive Silpuran® marketed by the company Wacker.

[0104] If necessary, a hydrogel layer 300 can cover the electrodes 200 ([Fig.2]). This is particularly advantageous in the case of gold or Ag / AgCl electrodes. The hydrogel layer is, for example, a conductive polymer layer. Alternatively, the hydrogel layer 300 is a layer comprising a polymer and electrically conductive elements, for example carbon or silver. The polymer is preferably a polysiloxane (silicone). The electrically conductive elements are in particular in the form of fibers, wires or particles (for example carbon fibers or silver particles).

[0105] For example, the hydrogel layer 300 may promote retention of the device on a subject without the need to apply pressure when placing the device and / or improve contact with the skin.

[0106] Furthermore, since the impedance range during measurement depends strongly on the skin-electrode interface, the use of a hydrogel layer makes it possible to remain within a range of a few hundred ohms. Advantageously, the hydrogel layer 300 will be placed on the electrodes 200 just before positioning the device on the subject's skin.

[0107] As shown in [Fig.7], the device may further comprise other connection and / or measurement elements. These elements may be, for example, a read-only memory 130 (also called ROM for 'Read Only Memory') and / or a humidity and / or temperature sensor 140.

[0108] The flexible substrate 100 may be a PCB (printed circuit board), in particular a flexible printed circuit (also called Flex PCB or flex circuit).

[0109] According to a particular embodiment, an adhesive film 600 can be positioned opposite the second main face of the substrate in order to be able to stick the device previously described on a subject or an object, and in particular on the skin of a subject (FIGS. 8A and 8B). The device is thus held on the subject.

[0110] The adhesive film 600 advantageously has a sufficient thickness to avoid producing folds when sticking the device to a subject and thus ensure good contact between the device and the skin.

[0111] The adhesive film is, for example, a bandage.

[0112] For example, it may be a dressing marketed under one of the following references: Comfeel Plus ([Fig.8A]), Flexcon NWP 240, or Adhex P1505 or Adhex P917 ([Fig.8B]).

[0113] According to the second embodiment variant, which can be combined with the first embodiment variant, adhesive zones 500 are positioned between the electrodes 200, so as to form an alternation of adhesive zones 500 and electrodes 200 ( [Fig.9]). The adhesive zones 500 are electrically insulating, to avoid short circuits. The adhesive zones 500 and the electrodes 200 cover the flexible substrate 100. The electrodes 200 and the adhesive zones 500 are positioned side by side. Preferably, the adhesive zones 500 do not cover the electrodes 200 in order to have the entire surface of the electrodes 200 accessible for the bioimpedance measurement.

[0114] The adhesive zones 500 have a first main face intended to be in contact with the subject, and in particular the subject's skin, and a second main face positioned opposite the flexible substrate 100.

[0115] The adhesive areas 500 may be formed by printing on the flexible substrate 100 or they may be transferred onto the flexible substrate 100. They are preferably formed by printing to allow better alignment of the adhesive areas 500 / electrodes 200.

[0116] The adhesive zones 500 have a width for example between 0.5 and 1.5 mm. The adhesive zones 500 may have identical or different widths. The thickness of the adhesive zones 500 is for example between 10 and 120 μm. All the adhesive zones 500 advantageously have the same thickness. The adhesive zones 500 have a thickness identical or similar to the thickness of the electrodes 200 in order to promote good contact with the skin not only for measurement but also for adhesion.

[0117] The material forming the adhesive zones 500 is, for example, a (meth)acrylate or a polysiloxane (also called silicone).

[0118] It may be a double-sided adhesive such as the adhesive marketed by the company 3M under the reference 2477P.

[0119] In order to compare the adhesion of different devices, a glass substrate coated by silicone (also called skin phantom) was used. The devices used for are as follows: one device has adhesive areas 500 between the electrodes 200 and another device has no adhesive areas. The electrodes 200 are electrodes obtained from an Ag / C / AgCl ink covered with gel (3 superimposed layers). Silver allows routing to the PCB. After a day, the device without adhesive areas is peeled off while the device with adhesive areas is perfectly stuck. It remains stuck for a week. The durability is significantly improved by the addition of adhesive areas 500.

[0120] According to an advantageous embodiment, an adhesive encapsulation layer is positioned on the substrate opposite the electrically conductive lines 120. In [Fig. 10], the adhesive encapsulation layer is represented by dotted lines. This adhesive encapsulation layer makes it possible to improve the duration of adhesion of the device to the silicone-coated glass substrate for 7 days. The encapsulation layer advantageously makes it possible to insulate and protect the electrically conductive lines 120.

[0121] The adhesive zones 500 may comprise cavities at its first face in order to contain a fluid, in particular a bodily fluid.

[0122] The adhesive areas 500 may comprise through holes 510 extending from the first face to the second face of the adhesive areas 500 (FIGS. 11, 12A and 12B). The through holes 510 allow a fluid, such as a bodily fluid, and in particular sweat, to be evacuated. Alternatively, they may be slots.

[0123] The holes 510 pass through at least the adhesive areas 500 and, preferably, the flexible substrate 100.

[0124] The through holes 510 are positioned between the electrodes 200.

[0125] They can be made by drilling and / or cutting.

[0126] The through holes 510 have, for example, a diameter of a few hundred micrometers (for example 250 μm). The holes 510 may be arranged regularly or irregularly. Preferably, they are arranged regularly. They are, for example, positioned every 500 μm.

[0127] The wall of the through holes 510 may have been subjected to a treatment in order to make it more hydrophilic. For example, this may be a plasma treatment (O2 plasma in particular), a UV-Ozone treatment or a polymer treatment.

[0128] It is also possible to carry out a hydrophobic treatment between the holes or between the electrodes in order to dewet and / or encourage the fluid (sweat in particular) to go into the holes 510. The treatment can be a plasma treatment or a fluorinated SAM treatment.

[0129] The adhesive areas 500 may comprise an adhesive material and elements capable of forming barriers intended to prevent the diffusion of a fluid from a electrode to an adjacent electrode.

[0130] An adhesive film 600 is advantageously positioned on the second face of the flexible substrate 100. The adhesive film has a surface area greater than the surface area of ​​the substrate in order to be able to adhere to the subject, in particular to the subject's skin ([Fig.l 1]).

[0131] Such a device can be manufactured according to the following steps: - Providing a flexible substrate 100 having a first main face and a second main face, - Forming electrodes 200 on the first main face of the flexible substrate 100, the electrodes locally covering the flexible substrate 100, - Form adhesive zones 500 between the electrodes 200, - Forming holes 500 passing through the adhesive zones 500 and, preferably, the substrate 100, and / or forming cavities at the second face of the adhesive zones 500 and / or forming elements made of a material other than the material forming the adhesive zones 500, arranged so as to prevent the creation of a continuous fluid path between two adjacent electrodes, - Where appropriate, possibly carry out a treatment to make the walls of the holes 510 hydrophilic or to increase their hydrophilic character, and / or carry out a hydrophobic treatment around the holes and / or around the electrodes to promote the concentration of the fluid between the electrodes and / or promote the insertion of the fluid into the less hydrophobic holes 510, - Optionally, position an adhesive film 600 on the second main face of the flexible substrate 100.

[0132] The device could also be manufactured according to the following steps: - Providing an intermediate substrate locally covered by adhesive zones 500, - Forming holes 500 passing through the adhesive zones 500 and / or forming cavities at the second face of the adhesive zones 500 and / or forming elements made of a material other than the material forming the adhesive zones 500, arranged so as to prevent the creation of a continuous fluid path between two adjacent electrodes, - If necessary, possibly carry out a treatment to make the walls of the 510 holes hydrophilic or to increase their hydrophilic character, - Position electrodes 200 (preferably 4 electrodes) between the adhesive zones 500, whereby an assembly is obtained comprising an alternation of adhesive zones 500 and electrodes 200, - Providing a flexible substrate 100 comprising a polymer material 110 and, preferably, electrically conductive lines 1210, and assembling it with the previously obtained assembly, by electrically connecting the electrodes 200 and the electrically conductive lines 120 where appropriate, - Preferably, position an adhesive film 600 on the second main face of the flexible substrate 100.

[0133] According to the third embodiment variant, which can be combined with the first embodiment variant and / or with the second embodiment variant, the device comprises a flexible substrate 100, one of the faces of which is covered by electrodes 200 and the other face is covered by an absorbent element 700. Holes pass through the substrate 100 from one side to the other in order to create a flow path to the absorbent element 700. Preferably, adhesive zones 500 are positioned between the electrodes 200 ([Fig. 13]).

[0134] The absorbent element 700 is chosen so as to be able to absorb fluids. Its volume can increase by a factor of 1 / 4, or even by a factor of 2 by absorption of the fluid.

[0135] Preferably, the absorbent element 700 is polydimethylsiloxane (PDMS), cellulose or a derivative thereof.

[0136] The absorbent element 700 may be adhesive. The adhesive element has a surface area greater than that of the substrate 100.

[0137] In the case where the absorbent element is not adhesive, it is advantageously positioned between the second main face of the substrate 100 and the adhesive element 600 ([Fig. 14]). According to an advantageous variant, a part of the absorbent element is positioned between the second main face of the substrate 100 and the adhesive element 600 and another part of the absorbent element penetrates into the holes 510 ([Fig. 15]).

[0138] The absorbent element 700 and the adhesive film 600 may be integral and form a so-called hydrocolloid dressing.

[0139] The absorbent element 700 advantageously has a surface area smaller than the surface area of ​​the adhesive film 600 to allow the adhesive film 600 to adhere to the skin.

[0140] Such a device can be manufactured according to the following steps: - Providing a flexible substrate 100 having a first main face and a second main face, - Forming electrodes 200 on the first main face of the flexible substrate 100, the electrodes locally covering the flexible substrate 100, - Preferably, form adhesive zones 500 between the electrodes 200, - Form holes 500 passing through the substrate 100, and where appropriate, the adhesive areas 500, - Optionally, carry out a treatment to make the walls of the 510 holes hydrophilic or to increase their hydrophilic character, - Position an absorbent element 700 then an adhesive film 600 on the second main face of the flexible substrate 100 or position a hydrocolloid dressing on the second main face of the flexible substrate 100.

[0141] In particular, as shown in [Fig. 14], the device may be a dressing to perform bioimpedance measurements on a subject. The device includes: - a 600 adhesive film, - an absorbent element 700, - a flexible substrate 100, which may be formed from a polymer material 110 and electrically conductive lines 120, - electrodes 200, preferably two or four electrodes, - adhesive zones 500 being preferably positioned between the electrodes 200, the electrodes 200 and the adhesive zones 500 covering the flexible substrate 100, so as to form an alternation of adhesive zones 500 and electrodes 200, the adhesive zones 500 having a first face intended to be in contact with the subject, - holes 510 passing through the flexible substrate 100, and where appropriate the adhesive zones 500, so as to allow the absorption of a fluid, for example a bodily fluid such as sweat.

[0142] The device can be used to measure various physiological parameters: electrocardiogram (ECG), electroencephalogram (EGG), electromyogram (EMG), or even resistance of biological tissues by bioimpedance. In particular, it allows, thanks to a local measurement of bioimpedance on the skin, to determine the quantity of water in the dermis and therefore the overall hydration rate of the individual. For this, so-called 4-point impedance spectroscopy (i.e. 4 electrodes) will be advantageously used. This makes it possible to limit the impact of the skin / electrode contact impedance.

[0143] Two electrodes are used to inject a current (microcurrent) and two electrodes are used to measure the voltage.

[0144] The frequencies are preferably between 100kHz and 1MHz to minimize artifacts.

[0145] The impedance range depends on the interface with the skin. The use of a conductive hydrogel makes it possible to maintain a range of a few hundred ohms.

[0146] In particular, the bioimpedance measurement method, used for example to measure the hydration rate of a subject or an object, comprises the following steps: - position, on the skin of a subject, a bioimpedance measuring device as described previously, - apply a current between the two distal electrodes, - measure the voltage between the two proximal electrodes, - calculate the impedance from the applied current and the measured voltage and determine the hydration rate of the subject or object.

[0147] Various embodiments and variations have been described. Those skilled in the art will understand that certain features of these various embodiments and variations could be combined, and other variations will occur to those skilled in the art.

[0148] Finally, the practical implementation of the embodiments and variants described is within the reach of those skilled in the art from the functional indications given above.

Claims

Claims

1. A method of manufacturing a bioimpedance measuring device comprising the following steps: - Providing a flexible substrate (100) comprising a polymer material (110) and electrically conductive lines (120), - Forming electrodes (200), preferably four electrodes, on the flexible substrate (100), the electrodes (200) being electrically connected to the conductive lines (120), the electrodes (200) being formed by printing, photolithography or transfer of an electrically conductive adhesive material.

2. Method according to claim 1, characterized in that the electrically conductive lines (120) are made of silver, preferably printed silver, or gold.

3. Method according to one of the preceding claims, characterized in that the transfer of the electrically conductive adhesive material is carried out by means of a transparent transfer layer (270).

4. Method according to any one of the preceding claims, characterized in that the electrodes (200) are formed by transferring an element to be transferred (220) in an electrically conductive adhesive material, comprising a first part having the shape of the electrodes (200) and a second part (210) intended to serve as a support during the transfer.

5. Method according to claims 3 and 4, characterized in that the transfer of the electrically conductive adhesive material is carried out according to the following sub-steps: - pre-cutting the element to be transferred (220) in a film of electrically conductive adhesive material (250), - positioning the element to be transferred (220) on the transparent transfer layer (270), preferably made of a fluoropolymer, - gluing the first part having the shape of the electrodes (200) on the flexible substrate (100), - separating the first part having the shape of the electrodes (200) from the second part (210) and from the transparent transfer layer (270), whereby the electrodes (200) are transferred to the flexible substrate (100).

6. A bioimpedance measuring device comprising: - a flexible substrate (100) comprising a polymer material (110) and electrically conductive lines (120), - electrodes (200), preferably four electrodes, arranged on the flexible substrate (100), the electrodes (200) being electrically connected to the conductive lines (120), the electrodes (200) being made of an electrically conductive adhesive material, a printed electrically conductive material or an electrically conductive material deposited by photolithography.

7. Device according to claim 6, characterized in that the electrically conductive lines (120) are made of printed silver.

8. Device according to one of claims 6 and 7, characterized in that the polymer material (110) is thermoplastic polyurethane, polyimide, silicone, polyethylene teraphthalate or polyamide.

9. Device according to one of claims 6 to 8, characterized in that the electrodes (200) made of a printed electrically conductive material are Ag / AgCl electrodes.

10. Device according to one of claims 6 to 8, characterized in that the electrodes (200) made of an electrically conductive adhesive material are made of a composite material comprising a polymer chosen from (meth)acrylates, polysiloxanes and their mixtures and an electrically conductive element, preferably particles, for example carbon particles, and / or an electrically conductive polymer, for example polyaniline or poly(3,4-ethylenedioxythiophene).

11. A method for measuring bioimpedance of a subject comprising the following steps: - positioning, on the skin of a subject, a device comprising a flexible substrate (100) and four electrodes (200) arranged on the flexible substrate (100), the flexible substrate (100) comprising a polymer material (110) and electrically conductive lines (120), the four electrodes (200) being electrically connected to the electrically conductive lines (120), the four electrodes (200) comprising two distal electrodes and two proximal electrodes, the electrodes (200) being made of an electrically conductive adhesive material, a printed electrically conductive material or a material deposited by photolithography, - applying a current between the two distal electrodes, - measuring the voltage between the two proximal electrodes, - calculating the impedance from the applied current and the measured voltage and determining, for example,the subject's hydration rate.,

12. Method according to claim 11, characterized in that the electrodes (200) are made of a composite material comprising a polymer chosen from (meth)acrylates, polysiloxanes and their mixtures and an electrically conductive element, preferably particles, for example carbon particles, and / or an electrically conductive polymer, for example polyaniline or poly(3,4-ethylenedioxythiophene).

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