Sensor for measuring a bioelectronic signal

Abstract

The present invention relates to a sensor for measuring a bioelectric signal, wherein the sensor comprises an electrode and an hydrogel in contact with the electrode, characterized in that the hydrogel comprises: an alginate salt; a copolymer of acrylamide and of at least one of alkyl-methacrylate monomer, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons; a surfactant; and a lithium salt.

Description

SENSOR FOR MEASURING A BIOELECTRONIC SIGNALTechnical field

[0001] The present invention is related to sensors for measuring a bioelectronic signal and to a method of preparation of such sensor.Background

[0002] In the field of acute and critical care medicine, the utilization of electroencephalography (EEG) is pivotal for the diagnosis and management of neurological conditions that require immediate intervention, such as seizures, status epilepticus, coma, and acute brain injuries. Despite its significance, the application of emergent EEG faces considerable challenges that affect its effectiveness and timeliness, impacting patient outcomes adversely.

[0003] The primary issue is the limited accessibility of EEG equipment and professionals trained in its set up and interpretation. This technology and expertise are not ubiquitously available, especially in smaller or less specialized healthcare facilities and rural areas. As a result, there is often a significant delay in the initiation of EEG monitoring for patients who present with acute neurological symptoms, which can be detrimental, particularly in conditions where every minute counts.

[0004] Moreover, the urgency required in emergency neurological care exacerbates the need for rapid deployment of EEG. Time delays in setting up and interpreting EEG can lead to delayed diagnosis and management, increasing the risk of poor neurological outcomes. Traditional EEG setup is time-consuming, involving the precise placement of multiple electrodes on thepatient's scalp, a process that becomes impractical in emergent situations where time is a scarce resource.

[0005] To address these formidable challenges, several solutions could be proposed. Developing portable, user-friendly EEG devices that can be rapidly deployed at the bedside by healthcare professionals with minimal training could significantly reduce setup times and make EEG more accessible.

[0006] EEG devices comprise electrodes electrically connected to a recording apparatus. The electrodes can be held on a scalp or on a skin by various means.

[0007] Conventional electrodes are usually described as "wet" because of the electrolytic gel necessarily associated with their use. Small disc electrodes are the most used to collect the signal. These are held in place by either an electrode cap or by using adhesive paste. Electrode may have various kind of shapes and can be made of multiple materials. A preferred electrode is a sintered silver / silver chloride (Ag / AgCI) due to its biocompatibility, non-polarizing nature, and low contact noise and baseline drift.

[0008] Despite being considered as the gold standard for EEG, “wet electrodes” present some drawbacks of long installation time and gel-related inconveniences.

[0009] Some limitations of the current procedure is the inconvenience caused to the patient due to the abrasive paste and the electrolytic gel, which, in addition to being sticky and making the scalp dirty, can cause skin irritation or infection. A proper amount of gel must be applied, as an excess of it can form electrical bridges between electrodes, inducing severe loss in spatial resolution. Additionally, once acceptable electrode impedances have been achieved, a countdown of a few hours begins until the gel dries, thus causing the transductive properties to disappear. Hence, gel-based electrodes are not practical for long-term measurements of 12 hours or more.

[0010] Vasconcelos et al. in “A Novel Dry Electrode Concept for Improved Wearing Comfort.”, Front Neurosci. 2021 Oct 18; 15:748100, and Lopez-Gordo et al. in “Dry EEG electrodes.”, Sensors (Basel). 2014 Jul 18; 14(7): 12847-70, disclose concepts of dry electrodes. Dry electrodes represent a radically different approach compared to gold standard wet electrodes, characterized by the absence of electrolyte fluid at the electrodescalp interface. Therefore, the coupling relies exclusively on the skinelectrode interface and the mechanical force exerted thereat.

[0011] A disadvantage of dry electrodes in which neither conductive gel nor abrasive paste are used is a larger electrode impedance. Typical electrode-skin impedance range between 150 to 200 kQ before and 5 to 10 kQ after gel application, respectively.

[0012] Guang-Li Li et al. in « Review of semi-dry electrodes for EEG recording.”, J Neural Eng. 2020 Oct 23;17(5):051004 describe various concepts of semi-dry electrodes. Those kinds of electrodes bridge the gap between typical wet and dry designs, retaining the advantages of both while addressing most of their respective drawbacks. The small amount of electrolyte prevents dirtying the hair and prevent short circuits, while also hydrating the scalp locally. This reduces the electrode / scalp impedance and effectively couples the electrode to the scalp. Benefiting from the formation of a relatively stable interface, semi-dry electrodes are less sensitive to electromagnetic interference and motion artifacts. Moreover, they are as easy to set up as dry electrodes, and there is no need to clean the hair after recording.

[0013] The first generation of semi-dry electrodes can be characterized by their release of a small amount of electrolyte fluid from a reservoir to the scalp when triggered under a specific pressure. The first "quasi-dry" concept was first proposed in 2013 with a novel Ag / AgCl-coated polyurethane (PU)-based design. The electrode reservoir flexibility ensured that a defined amount of 30 to 200 pl of electrolyte liquid could be released, wetting the skinlocally. EEG signals comparable to standard Ag / AgCI wet electrodes were recorded while avoiding soiling of the subjects' hair and reducing the risk of short circuits. However, the repeated electrode deformation under pressure increases the risk of coating failure.

[0014] Following a similar design principle, semi-dry concepts comprising microporous titanium, (Ti) soft conductive bristles, flexible multi-layers, hydrogel, and a micro-seepage sponge have been proposed. Regarding the Ti-based electrodes, despite being able to establish a reliable contact interface with a low and stable impedance, microporous Ti is expensive and very delicate to manufacture. Furthermore, the electrochemical polarization and corrosion of the Ti plate will inevitably occur in physiological saline, affecting the baseline stability and introducing low-frequency noise to the signals.

[0015] There are multiple other designs that have been proposed, relying on different materials and concepts. However, all of them release the electrolyte fluid depending on the applied pressure. This actuation may lead to uncontrolled and inconstant release. Therefore, impedance variation and signal instability are unavoidable.

[0016] The second-generation semi-dry electrodes use the capillary force of porous materials to achieve continuous and controlled electrolyte release instead of inconstant pressure.

[0017] Some proposed pin-shaped designs of electrodes using polymer wicks as the core electrolyte-permeable material such as polycarbonate-based wicks showed good mechanical properties with a cost-effective manufacturing process. A sponge soaked with specific hydrating solution or saline was placed at the back of the wick and acted as a reservoir. A chloriding silver wire was usually inserted in the sponge for signal transduction. Under capillary action, the hydration solution was continuously released to the skin without constantly pressing the reservoir. The electrodesshowed an automatic release of the solution, enabling a low average interface impedance of 37 ± 11 kQ for 7 hours of recording.

[0018] In addition to polymer wicks, porous ceramic wicks have been used as an electrolyte permeable material. The obtained interface impedance was of 22.2 ± 8.5 kQ and the electrode showed excellent nonpolarizable properties with a low off-set voltage of 0.58 mV and a negligible potential drift of 2.9 ± 1.4 pV. However, this is a complicated multi-part device, and the ceramic wicks are very stiff, potentially making the subjects uncomfortable.

[0019] Double-layer hydrogels have been investigated to find better compromises between electrical, swelling, and mechanical properties. An example of such double layer hydrogel structure is disclosed in the document “Hydrogel electrodes with conductive and substrate-adhesive layers for non-invasive long-term EEG acquisition” by Xue et al. in “hydrogel electrodes with conductive and substrate adhesive layers for non-invasive long-term EEG acquisition” Microcrosystems & nanoengineering (2003)9:79. The electrode comprises:a conductive hydrogel with high conductivity, low skin-contact impedance, and high robustness, and;an adhesive hydrogel that can bond to glass or plastic substrates to reduce motion artifacts.

[0020] The conductive hydrogel comprises sodium alginate (SA) and acrylamide (AM), KCI, cross-linking agents including N,N-methylenebisacrylamide (MBAA) and CaSO4, initiators including APS and TEMED and finally PEDOT:PSS and glycerol.

[0021] The adhesive hydrogel was prepared with the same compounds but with lower amount of glycerol, less water, in absence of electrolyte and PEDOT:PSS.

[0022] The adhesive hydrogel layer has better mechanical and adhesive properties than the conductive hydrogel layer, so that the adhesive hydrogellayer helps to maintain the conducting hydrogel layer in its plastic EEG support.

[0023] Document from Sikdar Partha et al: “Recent advances in the synthesis of smart hydrogels”, Material advances, vol. 2, no 14, describes various kind of hydrogels, each one of them having their own specific applications.

[0024] Document from Xu Tengjiao et al.: “High-strain sensitive zwitterionic hydrogels with swelling-resistant and controllable rehydration for sustainable wearable sensor” Journal of Colloid and Interface science, vol.620, 1 August 2022, p. 14-23, describes hydrogel samples fabricated by heat-induced radical polymerization of acrylic acid (AA), octadecyl methacrylate (SMA), sulfobetaine methacrylate (SBMA) and N,N’-methylenebisacrylamide (MBA) in an aqueous solution containing Tween 80. The formed P(AA-SMA-SBMA) copolymers are chemically cross-linked by MBA resulting in 3D structures. The fabricated hydrogels possess high strain sensitivity which is applied to monitor both junction motion and subtle movement like breathing and pulse.

[0025] There is still a need for improved EEG electrodes with a comfortable and biocompatible interface with a skin or a scalp, wherein the interface provides good electrical and mechanical properties, and good water and electrolyte retention.Summary of the invention

[0026] The present invention aims to provide a sensor for measuring a bioelectronic signal which can offer a good compromise between comfort for the user and stability of the signal over a relatively long period of time.

[0027] According to a first aspect, the present invention relates to a sensor for measuring a bioelectric signal, wherein the sensor comprises an electrode, and an hydrogel in contact with the electrode, characterized in that the hydrogel comprises:An alginate salt;A copolymer of acrylamide and of at least one of alkyl-methacrylate monomer, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons;A surfactant; andA lithium salt.

[0028] The hydrogel utilized herein has advantageous mechanical properties and good water retention over a relatively long period of time, preferably more than 12 hours, and even more preferably during a few days, which reduces the need of removing of the electrodes by a specialized practitioner for replacing the hydrogel or rehydrating the hydrogel. Additionally, the mechanical properties of the hydrogel utilized herein provides a good comfort on a skin or a scalp. The hydrogel used herein presents good stretchable properties and advantageously presents self-healing ability, allowing to keep the hydrogel for a relatively long period. Also, the hydrogel provided herein has a relatively good ionic and electric conductivity with a relatively low impedance.

[0029] Preferably, the lithium salt is a halide salt, more preferably lithium chloride.

[0030] Preferably, the lithium salt is present in the hydrogel in an amount of 0.1 to 10 wt% in weight of the hydrogel.

[0031] Preferably, water is present in the hydrogel in an amount of 25 to 95 wt% in weight of the hydrogel, in some embodiments in an amount of 40 to 85 wt% in weight of the hydrogel.

[0032] Preferably, the surfactant is present in the hydrogel in an amount of 1 to 20 wt%, preferably between 1 and 15 wt%, more preferably between 1 wt% and 10 wt% in weight of the hydrogel.

[0033] Preferably, the copolymer is present in the hydrogel in an amount of 5 to 25 wt% in weight of the hydrogel.

[0034] Preferably the alginate is present in the hydrogel in an amount of 0.5 to 5 wt% in weight of the hydrogel.

[0035] Preferably, the copolymer comprises between 1 to 10 wt% of alkylmethacrylate monomer units in weight of the copolymer.

[0036] Preferably, the alginate and the acrylamide units in the copolymer are present in the hydrogel in a weight ratio comprised between 0.5:10 and 2:10.

[0037] Preferably, the hydrogel is obtained from a process comprising the steps of :Providing a mixture by mixing in an aqueous solution having a concentration of sodium chloride comprised between 0.1 and 1 mol / l;an amount of surfactant in a weight of the aqueous solution comprised between 1 to 10 wt% in weight of water;an amount of alginate comprised between 0.5 and 5 wt% in weight of water,an amount of acrylamide comprised between 5 to 25 wt% in weight of water, wherein the weight ratio of alginate on acrylamide is comprised between 0.5:10 and 1 :5;an amount of alkyl-methacrylate, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons, comprised between 0.5 and 5 mol% relative to the amount of acrylamide;a thermal initiator; andan accelerator;irradiating the mixture with UV light to initiate polymerization of a copolymer of acrylamide an alkyl-methacrylate;preferably incubating the irradiated mixture at a temperature comprised between -10°C to 100°C, preferably between 15°C to 70°C for at least 1 hour, preferably at least 10 hours;soaking the irradiated and incubated mixture in a solution of a lithium salt having a concentration comprised between 1 mol / l and 12 mol / l, preferably between 1 mol / l and 6 mol / l.

[0038] Preferably, the prior to the step of incubating the irradiated mixture, a prior step comprises pouring the irradiated mixture into a mold.

[0039] Optionally, after incubation of the hydrogel, the hydrogel is shaped and provided into a meshed support having an inner cavity with dimensions corresponding to the dimensions of the shaped hydrogel and the meshed support comprising the shaped hydrogel is immersed into the lithium salt solution for soaking.

[0040] Preferably, the sensor comprises an electrode support comprising a cavity for receiving the hydrogel.

[0041] Preferably, the electrode comprises a solid conductive electrode preferably selected from gold, silver, titanium orAg / AgCI, or a non-conductive material coated with a conductive layer such as gold or Ag / AgCl.

[0042] Preferably, the hydrogel is rehydratable, preferably with an aqueous solution of lithium salt.Brief description of the figures.

[0043] Fig. 1 a shows the coordinates of a set of sensors according to the International 10-20 system for encephalography recording.

[0044] Fig. 1b shows measured impedances of a set of twenty-one sensors placed on the head of a test subject with a controlled pressure distribution of each sensor against the scalp.

[0045] Fig. 2 shows the head of a test subject directly after removal of the sensors according to the invention utilized in a clinical test.

[0046] Fig. 3 shows an aspect of a shaped hydrogel according to an embodiment of the invention.Detailed description of the invention

[0047] The present invention is related to a sensor for measuring a bioelectric signal, such as a sensor for an electroencephalograph device. The sensor comprises an electrode, an electrode support and an hydrogel in contact with the electrode, characterized in that the hydrogel comprises:An alginate salt;A copolymer of acrylamide and of at least one of alkyl-methacrylate monomer, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons;A surfactant; andA lithium salt.

[0048] The electrode preferably comprises a solid conductive electrode, for example made of gold, silver, titanium or Ag / AgCl. It can also be a non-conductive material coated with a conductive layer such as gold or Ag / AgCl.

[0049] The sensor according to the invention preferably comprises an electrode support which comprises a cavity allowing the electrode to contact the hydrogel. In use, the cavity is opened on a skin or a scalp with the hydrogel in contact with the scalp or the skin. The electrode may be fixed in the electrode support either by injection overmolding, or by a mechanical or chemical assembly or a combination thereof. Its shape can be flat or cupshaped, meshed or plain.

[0050] Preferably, the hydrogel used herein is obtained from a process comprising the steps of:Providing a mixture by mixing in an aqueous solution having a concentration of sodium chloride comprised between 0.1 and 1 mol / l;an amount of surfactant in a weight of the aqueous solution comprised between 1 to 20 wt% in weight of water;an amount of alginate comprised between 0.5 and 5 wt% in weight of water;an amount of acrylamide comprised between 5 to 25 wt% in weight of water, wherein the weight ratio of alginate on acrylamide is comprised between 0.5:10 and 1 :5;an amount of alkyl-methacrylate, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons, comprised between 0.5 and 5 mol% relative to the amount of acrylamide;a thermal initiator;and an accelerator;irradiating the mixture with UV light to initiate polymerization of a copolymer of acrylamide an alkyl-methacrylate;preferably incubating the irradiated mixture at a temperature comprised between -10°C to 100°C, preferably between 15°C to 70°C for at least 1 hour, preferably at least 10 hours;soaking the irradiated and incubated mixture in a solution of a lithium salt having a concentration comprised between 1 mol / l and 12 mol / l, preferably between 1 mol / l and 6 mol / l.

[0051] Preferably, the initiator and the accelerator are provided in the mixture after having provided all of the other compounds in the mixture. The initiator is preferably ammonium persulfate (APS) and the accelerator is preferably N,N,N’,N’-tetramethylethylenediamine (TEMED). Alternative initiators and / or accelerators known by the skilled person for making a hydrogel can be used. The initiator and accelerator are used in small amounts relative to the alginate, acrylamide and alkyl-methacrylate.

[0052] In some embodiments, glycerol and PEDOT:PSS can be added in the composition of the hydrogel.

[0053] In the process of obtention of the hydrogel as described above, the surfactant utilized is preferably sodium dodecyl sulfate, and the alkylmethacrylate is preferably stearyl-methacrylate. Without being bounded by a theory, when stearyl methacrylate (SMA) is co-polymerized with acrylamide (AAm) in presence of sodium alginate and of a surfactant like SDS, the SDS forms micelles in water wherein hydrophobic chain segments of SMA units can grow while hydrophilic larger chains of AAm units grow in the aqueous solution. A copolymer of acrylamide and of stearyl methacrylate is thereby obtained wherein the copolymer comprises hydrophilic units of acrylamide and hydrophobic units of stearyl methacrylate, and wherein the copolymer is interpenetrated by alginate chains. The resulting Na-alginateZP(AAm-co-SMA) comprises a network P(AAm-co-SMA) reticulated by aggregations of stearyl-methacrylate units of the copolymer comprised in the SDS micelles. The size of the micelles can be optimized by temperature, pH or SDS concentration, preferably to increase their size and providing more sites for hydrophobic units of the copolymer, thereby providing more hydrophobic interactions at each reticulation sites, providing a more solid reticulation and better mechanical properties. Reticulation is preferably achieved by UV irradiation, preferably at a wavelength comprised between 170 to 380nm, more preferably 300 nm to 380 nm, in some embodiments at 365 nm.

[0054] Preferably, in the process for obtaining the hydrogel, prior to the step of incubating the irradiated mixture, a prior step comprises pouring the irradiated mixture into a mold. The mold can be designed to conform with the cavity of the electrode support. Alternatively, the irradiated mixture is poured directly into the cavity of the electrode support and then let under incubation.

[0055] After incubation, for example for 12 to 24 hours at room temperature, under ambient conditions, i.e. between 20°C and 25°C and room pressure, the irradiated and incubated mixture is soaked in an aqueous solution comprising preferably 1 to 6 mol / l of lithium chloride (LiCI), preferably for at least 20 hours, more preferably for at least 24 hours even more preferably for 48 hours.

[0056] In some embodiments, the soaking step with the solution of lithium salt can be performed for at least 36 hours under stirring and with at least three renewals of the lithium salt solution such as to remove or reducing the content of any eventual residual monomer.

[0057] The soaking and washing step may induce an uncontrolled isotropic swelling. This means that despite molding the hydrogels at the desired dimensions, during their synthesis, their washing may vary their shape in an unpredictable manner. Optionally, in an embodiment of the process for making the hydrogel, a meshed support comprising a cavity for holding the hydrogel and for allowing the solvent to circulate through the hydrogel while holding the hydrogel such as to prevent its deformation can be provided. Such a support can be obtained for example by 3D printing. Preferably, after incubation of the hydrogel, the hydrogel is shaped and provided into the meshed support having an inner cavity with dimensions corresponding to the dimensions of the shaped hydrogel and the meshed support comprising the shaped hydrogel is immersed into the lithium salt solution for soaking.

[0058] Mechanical properties of the hydrogel also depend on the concentration of LiCI in the solution used for soaking the hydrogel. Withoutbeing bounded by a theory, lithium chloride decreases electrostatic repulsion between hydrophilic groups of SDS, favorizing the growth of micelles and therefore, the reticulation strength of the network of the copolymer. Also, lithium ions have smaller radius than sodium ions and have a better bonding ability with carboxylate groups of alginate chains, thereby substituting the sodium ions of the alginates. Inter-chain aggregations are formed between several alginate polymers that are close to each other. In addition, Lithium ions polarize the water molecules and interferes with hydrophobic hydration of alginate polymers, which exposes the hydrophobic groups of the alginate chains. This results in the aggregation of the alginate chains and the physical cross-linking of the Li-Alginate network. The hydrogel is mainly crosslinked by physical interactions.

[0059] Preferably, the swollen hydrogel obtained after soaking in LiCI aqueous solution has a compressive Young’s modulus comprised between 2,5 and 10 kPa, preferably between 3 and 6 kPa.

[0060] Preferably, the hydrogel is reusable and rehydratable, preferably with an aqueous solution of lithium salt.

[0061] The hydrogel used herein also provides a good impedance, below 5 kQ, in some embodiments, even below 1 kQ. The impedance measurements were performed with an impedancemeter WAYNEKERR Precision Component Analyzer 6425.

[0062] In a preferred embodiment, the alginate salt is sodium alginate, the alginate is preferably present in the hydrogel in an amount of 0.5 to 5 wt% in weight of the hydrogel, preferably measurable by NMR preferably on a sample after 24 hours of soaking in an aqueous solution of LiCI.

[0063] The copolymer is preferably present in the hydrogel in an amount of 5 to 25 wt% in weight of the hydrogel, preferably measurable by NMR preferably after 24 hours of soaking in an aqueous solution of LiCI.

[0064] In the copolymer, the alkyl-methacrylate monomer preferably comprises a linear alkyl group comprising 10 to 30, more preferably 10 to 20 carbon atoms. In a preferred embodiment, the alkyl-methacrylate monomer is stearyl-methacrylate. The copolymer preferably comprises between 1 to 10 wt% of alkyl-methacrylate monomer units in weight of the copolymer, preferably measurable by NMR preferably after 24 hours of soaking in an aqueous solution of LiCI.

[0065] The surfactant comprises a polar hydrophilic group and an hydrophobic tail wherein the hydrophilic group preferably comprises sulfate or ammonium and the hydrophobic tail preferably comprises a linear alkyl group comprising 8 to 30 carbons. Preferably, the linear alkyl group of the hydrophobic tail of the surfactant comprises a similar number of carbon than the alkyl group of the alkyl-methacrylate. In a preferred embodiment, the surfactant is sodium dodecyl sulfate (SDS).

[0066] Preferably, the lithium salt is lithium chloride and is present in the hydrogel in an amount of 0.01 to 20 wt%, preferably 0.1 to 20 wt%, more preferably 1 wt% to 10 wt% in weight of the hydrogel measured by inductively coupled plasma (ICP) on a sample taken preferably after 24 hours of soaking in an aqueous solution of LiCI, wherein the water in the sample is removed, for example in an oven at 100°C and the remaining residue is burned.

[0067] Water is preferably present in the hydrogel in an amount of 40 wt% to 99 wt%, preferably between 50 wt% to 98 wt%, more preferably between 50 wt% to 95 wt% even more preferably between 50 wt% to 90 wt% in weight of the hydrogel measured preferably on a sample after 24 hours of soaking in an aqueous solution of LiCI, by weight loss at 100°C until constant weight.

[0068] The alginate in the hydrogel and the acrylamide units in the copolymer are present in the hydrogel in a weight ratio comprised between 0.5:10 and 1:5, preferably measurable by NMR preferably on a sample after 24 hours of soaking in an aqueous solution of LiCI.

[0069] Examples

[0070] Various compositions of hydrogel have been prepared according to the process described above with the amounts presented in table 1.Table 1

[0071] The six samples of table 1 were soaked in soaking solutions. Sample 1 was soaked in an aqueous solution comprising 1 mol / l of LiCI for 28 hours. Sample 2 was soaked in pure water for 24 hours and sample 3 was soaked in pure water for 6h35. Samples 4, 5 and 6 were soaked for 48 hours in aqueous solutions comprising respectively 1 mol / l, 2 mol / l and 3 mol / l of LiCI.

[0072] Before soaking, each sample was weighted three times, and the average weight was considered. Then at a starting time TO, the samples were soaked in their respective soaking solution. Each sample was removedseveral times from the soaking solution for weighting until the weight of hydrogel reached a plateau, indicating that the hydrogel has swollen.

[0073] Sample 1 was removed from the soaking solution after 28 hours, sample 2 was removed from the soaking solution after 24 hours, while sample 3 was removed from the soaking solution only after 6h35 as it started to desegregate.

[0074] From the time when the three sample were definitely removed from their soaking solution, the samples were let under ambient temperature (between 20°C to 25°C) and were weighted several times to follow the evolution of water release. After 28 hours of soaking, Sample 1 had its weight increased of 133% compared to its weight at TO. After 24 hours of soaking, sample 2 had its weight increased of 222% compared to its weight at TO. Sample 3 had its weight increased of 176% compared to its weight at TO.

[0075] After 19 hours of drying at ambient temperature, sample 1 only lost 9.5% of its weight relative to its weight at 24 hours after soaking. After 49 hours, the same sample 1 lost 22% of its weight relative to its weight after soaking. After 24 hours of drying at ambient temperature, Sample 2 lost 22% of its weight relative to its weight after soaking. After 50 hours of drying at ambient temperature, the same sample 2 lost 41 % of its weight relative to its weight after soaking. After 25 hours of drying, sample 3 lost 23% of its weight relative to its weight after soaking. After 44 hours, sample 3 lost 38 % of its weight relative to its weight after soaking.

[0076] Therefore, a better water retention has been obtained for the sample 1 that was soaked in a LiCI solution.

[0077] Also the sample 1 kept good mechanical properties, kept its initial shape and remained handy without being too sticky.

[0078] After 48 hours in the soaking solution comprising 1 mol / l of LiCI, the weight of sample 4 increased of 172 %. Following those 48 hours, sample 4 was let outside the soaking solution at ambient temperature and wasweighted after 18 hours of drying and lost 18 % of its weight relative to its weight just after soaking. At the same time, an impedance of 480 Q was measured.

[0079] After 48 hours in the soaking solution comprising 2 mol / l of LiCI, the weight of sample 5 increased of 153 %. Following those 48 hours, sample 5 was let outside the soaking solution at ambient temperature and was weighted after 18 hours of drying and lost 9.6 % of its weight relative to its weight just after soaking. At the same time, an impedance of 437 Q was measured. After 48 hours outside the soaking solution, sample 5 had lost 18.7 % of its weight.

[0080] After 48 hours in the soaking solution comprising 3 mol / l of LiCI, the weight of sample 6 increased of 188 %. Following those 48 hours, sample 6 was let outside the soaking solution at ambient temperature and was weighted after 18 hours of drying and lost only 6.8 % of its weight relative to its weight just after soaking. At the same time, an impedance of 250 Q was measured. After 48 hours outside the soaking solution, sample 6 had lost 14 % of its weight. After 7 days outside the soaking solution, the sample 6 conserved more than 60 % of its weight relative to its weight just after soaking, while sample 4 and sample 5 had their weight decreased well below 50 % relative to their weight just after soaking.

[0081] Sample 6 appeared to have the best mechanical properties, with the best water retention and the lowest impedance.

[0082] The Young modulus in compression of six samples of the hydrogel prepared according to example 6 was measured 28 hours after having removed the samples and having let them out of the soaking solution at ambient temperature. The average compression Young Modulus of those six samples prepared according to sample 6 was of 4.5 kPa with a standard deviation of 1 kPa. After compression, other samples made according to examples 4 and 5 were completely flattened or destroyed.

[0083] Therefore, the soaking solution of 3 mol / l of LiCI appears to be the best choice for the preparation of the hydrogel. Higher concentrations of LiCI would be also good for mechanical and electrical properties of the hydrogel but might become irritating for the skin.

[0084] Another experiment has been carried out to assess the residual acrylamide monomer content after the hydrogel synthesis but also, after the soaking step in the aqueous solution of 3 mol / l of LiCI.

[0085] Measurements of an acrylamide monomer sample, and of the hydrogels samples before the soaking step and after the soaking step mentioned above have been performed by Fourier-Transform Infrared Spectroscopy (FTIR). Semi-quantitative results shows that peaks corresponding to acrylamide monomer are present in the spectra of the sample of hydrogel before the soaking step and disappeared or were strongly reduced after the soaking step, while characteristic peaks of polyacrylamide have remained, suggesting an efficient polymerization, and a decrease of the amount of residual monomer in the hydrogel.

[0086] A clinical test has been realized by placing a setup of twenty-one sensors according to the invention on the head of a test subject. Each sensor comprised an electrode and a hydrogel in contact with the electrode, and an electrode support comprising a cavity for receiving the hydrogel. The hydrogel utilized in the sensors was the hydrogel according to sample 6. The fig. 1a presents coordinates according to the International 10-20 system for encephalography recording.

[0087] Interface impedances can be evaluated by neurologists according to four levels of signal quality: an impedance below 10 kQ is ideal; between 10 and 50 kQ is totally fine to read and is usually the quality achieved in practice; between 50-75 kQ is still readable but with some difficulties; and above 75 kQ is not readable anymore or not for a sufficient portion of the recording.

[0088] Fig. 1b shows measured impedance of the set of twenty-one sensors placed on the head of a test subject with a controlled pressure distribution of each electrode against the scalp. Seventeen sensors have an impedance of less than 10 kQ, including nine sensors below 5 kQ. Only four sensors on the twenty-one sensors showed an impedance higher than 10 kQ but still below 20 kQ.

[0089] Notably, those results were obtained at hairy locations with no skin preparation and in a few minutes (about 8 minutes) because of the mechanical properties of the hydrogel having a relatively high content of water, being less sticky and stiffer than prior art hydrogels used in EEG. This is particularly advantageous compared to prior art hydrogels used in wetsensors for EEG wherein the installation process of sensors over the head of the patient generally requires a specific training and may be very time consuming (i.e. generally 40 minutes of placement of twenty-one sensors mobilizing two expert technologists).

[0090] The resulting signal quality follows the same trend with a clear recording. The quality of the obtained signal by the sensors according to the invention is similar to the quality of the signal obtained by standard sensors utilized in EEG.

[0091] The Fig. 2 shows the head of the test subject after removal of the sensors. One can see that the tested locations are well haired and that those are neither wet nor soiled by the hydrogel or the fluid. This is another strong point for patients compared to current unpleasant and soiling installation and removal procedures. Notably, the comfort was significantly improved, and no pressure points were pointed out by the test subject after one hour of recording.

[0092] The fig. 3 shows an aspect of the hydrogel of example 6. The hydrogel can be sealed and stored for several days or weeks without losing its water content, offering realistic shelf conditions suitable for clinical context. The hydrogel saturated in water (i.e. directly after removal from the soakingsolution) was placed and stocked for seven days in a hermetic container at room temperature and at daily light exposure. Under these conditions, the hydrogel lost only less than 5% of its initial weight. Despite this loss of water, the hydrogel was still usable without rehydration in a sensor for EEG recording for at least 3 hours.

[0093] Sensors comprising the hydrogel described herein can be used for EEG electrodes or alternatively for other kind of electrode devices for everyday applications such as performance and wellness tracking for professional and amateur athletes, or anyone who wants to track their neurological state. This is part of the growing trend towards daily health monitoring. We can see this, for example, with connected watches, which are now certified as a medical device for cardiac monitoring.

[0094] The sensor according to the invention comprising the hydrogel such as described herein which is advantageously biocompatible, is well adapted for use as sensor that is aimed to be carried out by a person for a relatively long period of time without causing discomfort for the person. The hydrogel can be replaced less frequently and advantageously keeps its mechanical properties so that it can be rehydrated in a saline solution, preferably comprising LiCI, and can be reused.

[0095] The sensors according to the present invention can also be used for various applications involving the control of connected objects by thought (computer, industrial machines, robots, smartphones, etc.), known under the name of Brain-Computer Interface (BCI).

Claims

Claims1. Sensor for measuring a bioelectric signal, wherein the sensor comprises an electrode, and an hydrogel in contact with the electrode, characterized in that the hydrogel comprises:- An alginate salt;- A copolymer of acrylamide and of at least one of alkylmethacrylate monomer, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons;- A surfactant; and- A lithium salt.

2. Sensor according to claim 1 wherein the lithium salt is a halide salt, more preferably lithium chloride, preferably present in the hydrogel in an amount of 0.1 to 10 wt% in weight of the hydrogel.

3. Sensor according to claim 1 or 2, wherein water is present in the hydrogel in an amount of 25 to 95 wt% in weight of the hydrogel.

4. Sensor according to any one of the preceding claims, wherein the surfactant is present in the hydrogel in an amount of 1 to 20 wt% in weight of the hydrogel.

5. Sensor according to any one of the preceding claims, wherein the copolymer is present in the hydrogel in an amount of 5 to 25 wt% in weight of the hydrogel.

6. Sensor according to any one of the preceding claims, wherein the alginate is present in the hydrogel in an amount of 0.5 to 5 wt% in weight of the hydrogel.

7. Sensor according to any one of the preceding claims, wherein the copolymer comprises between 1 to 10 wt% of alkyl-methacrylate monomer units in weight of the copolymer.

8. Sensor according to any one of the preceding claims wherein the alginate salt in the hydrogel and the acrylamide units in the copolymer are present in the hydrogel in a weight ratio comprised between 0.5:10 and 1 :5.

9. Sensor according to any one of the preceding claims, wherein the hydrogel is obtained from a process comprising the steps of :o Providing a mixture by mixing in an aqueous solution having a concentration of sodium chloride comprised between 0.1 and 1 mol / l;o an amount of surfactant in a weight of the aqueous solution comprised between 1 to 20 wt% in weight of water;o an amount of alginate comprised between 0.5 and 5 wt% in weight of water,o an amount of acrylamide comprised between 5 to 25 wt% in weight of water, wherein the weight ratio of alginate on acrylamide is comprised between 0.5:10 and 1:5;o an amount of alkyl-methacrylate, wherein the alkyl group is preferably linear and comprises 10 to 30 carbons, comprised between 0.5 and 5 mol% relative to the amount of acrylamide;o a thermal initiator; ando an accelerator;- irradiating the mixture with UV light to initiate polymerization of a copolymer of acrylamide an alkyl-methacrylate;- preferably incubating the irradiated mixture at a temperature comprised between -10°C to 100°C, preferably 15°C to 70°C for at least 1 hour, preferably at least 10 hours;- soaking the irradiated and incubated mixture in a solution of a lithium salt having a concentration comprised between 1 mol / l and 12 mol / l, preferably between 1 mol / l and 6 mol / l.

10. Sensor according to claim 9, wherein prior to the step of incubating the irradiated mixture, a prior step comprises pouring the irradiated mixture into a mold.

11. Sensor according to any one of the preceding claims, comprising an electrode support comprising a cavity for receiving the hydrogel.

12. Sensor according to any one of the preceding claims wherein the electrode comprises a solid conductive electrode preferably selected from gold, silver, titanium or Ag / AgCI, or a non-conductive material coated with a conductive layer such as gold or Ag / AgCI.

13. Sensor according to any one of the preceding claims, wherein the hydrogel is rehydratable, preferably with an aqueous solution of lithium salt.

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