KR20230105805A - Ultrathin micro needle type electrode, manufacturing method for the same and attaching method for the same - Google Patents

Abstract

The present application relates to an ultra-thin type microneedle electrode comprising: a sacrificial layer of a needle shape comprising a water-soluble polymer; a support layer formed on the sacrificial layer of the needle shape; and an electrode layer formed on the support layer. Therefore, the present invention may not cause an inconvenience in a livelihood.

Description

Ultra-thin microneedle electrode, manufacturing method thereof, and attachment method thereof

The present application relates to an ultra-thin microneedle electrode and a manufacturing method thereof.

Recently, with the development of wearable technology based on bioelectronic devices, a basis for constantly measuring electrical signals or physiological signals from people in real time has been established, enabling measurement of a wide variety of signals on human skin. For example, brain wave signals (EEG), heart signals (ECG), muscle signals (EMG), etc. can be measured as electrical signals from human skin, and metabolites such as uric acid, lactic acid, and glucose can be measured as physiological signals. It also measures or collects sweat to analyze its various constituents. In order to measure these biosignals from the skin, an important thing is an electrode part that connects a person's skin and an external device.

In order to successfully measure these bioelectrical signals, the electrical impedance between the electrode and the skin is fundamentally low, so that the electrical signal must be sufficiently transmitted from the human to the electrode without being hindered. However, the stratum corneum, which is the outermost layer of human skin, is a dead cell that does not conduct electricity well and acts as an insulator to block electrical signals, resulting in a very high impedance, thereby lowering the accuracy of measurement. In addition, in the case of biophysiological signals, it is possible to identify various chemical substances contained in it when an abundant amount of body fluid or sweat can be brought into contact with the electrodes. There is a problem of lowering the accuracy of the measured data by preventing the collection of an abundant amount of bodily fluid.

As an existing method for solving the barrier effect of the stratum corneum, there is a microneedle electrode. When the microneedle electrode is attached to the skin, the protruding needle part penetrates the stratum corneum of the skin and is positioned. Existing microneedle electrodes can successfully measure bioelectrical signals by drastically lowering electrical impedance by piercing the stratum corneum, and are advantageous in terms of physiological signal measurement as they can be contacted with richer body fluids under the stratum corneum. However, microneedle electrodes require an appropriate level of continuous pressure and an additional fixing method for the needle electrode to penetrate the stratum corneum and attach to the skin, and there is a continuous accumulation of pain and discomfort from electrode attachment, and additional weighty additional There are problems such as difficulty in long-term use due to fixation devices and persistent pain.

Korean Patent Registration No. 10-1906590, which is the background of the present application, discloses a needle structure and a bio-signal measuring device having the same.

The present application provides an ultra-thin microneedle electrode and a manufacturing method thereof to solve the above-described problems of the prior art.

In addition, a biosignal measurement method using the ultra-thin microneedle electrode is provided.

However, the technical problem to be achieved by the embodiments of the present application is not limited to the technical problems described above, and other technical problems may exist.

As a technical means for achieving the above technical problem, the first aspect of the present application includes a needle-shaped sacrificial layer containing a water-soluble polymer, a support layer formed on the needle-shaped sacrificial layer, and an electrode layer formed on the support layer. To provide an ultra-thin microneedle electrode.

According to one embodiment of the present application, the needle-shaped portion of the electrode layer may penetrate the surface of the biological tissue and be fixed on the biological tissue, but is not limited thereto.

According to one embodiment of the present application, after the ultra-thin microneedle electrode is fixed on a living tissue, the needle-shaped sacrificial layer may be removed by moisture supplied from the outside, but is not limited thereto.

According to one embodiment of the present application, the water-soluble polymer is a water-soluble polymer selected from the group consisting of polyvinyl alcohol (PVA), poly acrylic acid (PAA), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), and combinations thereof It may include, but is not limited thereto.

According to one embodiment of the present application, the maximum height of the needle shape may be 50 μm to 1,000 μm, but is not limited thereto.

According to one embodiment of the present application, an adhesive layer may be formed on the electrode layer, but is not limited thereto.

According to one embodiment of the present application, the adhesive layer may include one selected from the group consisting of acrylate, silicone, epoxy, and combinations thereof, but is not limited thereto.

According to one embodiment of the present application, the support layer may include a material having biocompatibility, but is not limited thereto.

According to one embodiment of the present application, the supporting layer may have CVD compatibility, but is not limited thereto.

According to one embodiment of the present application, the support layer is parylene, poly (1,3,5-trivinyl trimethyl cyclotrisiloxane) (poly (1,3,5-trivinyl trimethyl cyclotrisiloxane)), and these It may include one selected from the group consisting of combinations of, but is not limited thereto.

According to one embodiment of the present application, the thickness of the support layer may be 10 nm to 10 μm, but is not limited thereto:

According to one embodiment of the present application, the electrode layer includes one selected from the group consisting of Au, Cr, Pt, Ag, Fe, Cu, Ni, Ti, graphene, carbon nanotubes, conductive polymers, and combinations thereof. It can be done, but is not limited thereto.

According to one embodiment of the present application, the conductive polymer is PEDOT (poly (3,4-ethylene dioxythiophene)), polyaniline (polyaniline), poly (para-phenylene vinylene) (poly (para-phenylene vinylene), poly (para-phenylene) (poly(para-phenylene)), polyacetylene, polypyrrole, polythiophene, poly(p-phenylene sulfide), polyaniline, and combinations thereof It may include those selected from, but is not limited thereto.

According to one embodiment of the present application, the ultra-thin microneedle electrode is an electroencephalogram (EEG), a heart signal (electrocardiogram, ECG), a muscle signal (electromyogram, EMG), a concentration of uric acid, a concentration of lactic acid, a concentration of glucose, A component selected from the group consisting of a component in body fluid, a component in saliva, and a combination thereof may be measured, but is not limited thereto.

In addition, the second aspect of the present invention includes the steps of preparing a needle-shaped water-soluble polymer sacrificial layer, forming a support layer on the water-soluble polymer sacrificial layer, and forming an electrode layer on the support layer , A method for manufacturing ultra-thin microneedle electrodes is provided.

According to one embodiment of the present application, the step of forming the supporting layer may be performed by a chemical vapor deposition (CVD) method, but is not limited thereto.

According to one embodiment of the present application, the step of forming the electrode layer is selected from the group consisting of physical vapor deposition (PVD), sputtering, CVD, atomic layer deposition (ALD), dip coating, spin coating, and combinations thereof It may be performed by a method including, but is not limited thereto.

According to one embodiment of the present application, it may further include forming an adhesive layer on the electrode layer, but is not limited thereto.

A third aspect of the present application includes disposing the electrode layer of the ultra-thin microneedle electrode according to the first aspect of the present application on the biological tissue so as to penetrate the biological tissue, supplying moisture to the sacrificial layer of the ultra-thin microneedle electrode to It provides a biosignal measuring method comprising removing the sacrificial layer and measuring the biosignal through an electrode layer disposed on the skin.

According to one embodiment of the present application, the biosignal is an electroencephalogram (EEG), a heart signal (electrocardiogram, ECG), a muscle signal (electromyogram, EMG), a concentration of uric acid, a concentration of lactic acid, a concentration of glucose, a body fluid components, components in saliva, and those selected from the group consisting of combinations thereof, but are not limited thereto.

The above-described problem solving means are merely exemplary and should not be construed as intended to limit the present disclosure. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and detailed description of the invention.

The ultra-thin microneedle electrode according to the present invention has a support layer and an electrode formed on a needle-shaped sacrificial layer containing a water-soluble polymer. In the past, a very thin and flexible electrode, which was difficult to penetrate the stratum corneum, can penetrate the stratum corneum and be fixed. It can have a low skin-to-electrode impedance and can come into contact with more types of body fluids.

In addition, as the electrode layer is implemented in the form of a thin film, the surface of the electrode layer of the ultra-thin microneedle electrode according to the present invention can be made curved, irregular, and flexible, so that it can be suitably attached to human skin, compared to conventional microneedle electrodes. It is less painful and may not cause any discomfort in life.

In addition, since the ultra-thin microneedle electrode according to the present invention has low impedance without causing discomfort in daily life with little pain and is flexibly attached to the skin, real-time and long-term biosignal measurement is possible, which is difficult with conventional skin-attached electrodes. . As the real-time and long-term bio-signal measurement draws attention in the healthcare monitoring field, the ultra-thin microneedle electrode is advantageous for real-time monitoring compared to conventional skin-attached electrodes.

In addition, the ultra-thin microneedle electrode is fixed by penetrating the stratum corneum through the sacrificial layer, and then the sacrificial layer is removed by water. At this time, the fixed electrode layer is fixed on living tissue without an additional fixing device. state can exist.

However, the effects obtainable herein are not limited to the effects described above, and other effects may exist.

1 is a schematic diagram of an ultra-thin microneedle electrode according to one embodiment of the present application.
2 is a schematic diagram of an ultra-thin microneedle electrode according to one embodiment of the present application.
3 is a process of fixing an ultra-thin microneedle electrode according to one embodiment of the present application onto a biological tissue.
4 is a flowchart illustrating a method of manufacturing an ultra-thin microneedle electrode according to an embodiment of the present disclosure.
5 is a cross-sectional view of an ultra-thin microneedle electrode according to an embodiment of the present disclosure.
6 is a photograph of a substrate on which an ultra-thin microneedle electrode is formed according to an embodiment of the present disclosure.
7 (a) to (c) are photographs of ultra-thin microneedle electrodes according to an embodiment of the present application.
8 (a) shows the skin to which the conventional microneedle is attached, (b) shows the skin to which the ultra-thin microneedle electrode according to the present application is attached, and (c) and (d) show the conventional microneedle and the ultra-thin electrode according to the present application. It is a graph of the impedance between the microneedle electrode and the skin.
9 (a) to (c) are photographs with conventional microneedle electrodes attached, and (d) to (f) are photographs with ultra-thin microneedle electrodes according to the present application attached.
Figure 10 (a) is a graph measuring EEG using an ultra-thin microneedle electrode according to an embodiment of the present application, and (b) is a graph measuring EMG.

Hereinafter, embodiments of the present application will be described in detail so that those skilled in the art can easily practice with reference to the accompanying drawings. However, the present disclosure may be implemented in many different forms and is not limited to the embodiments described herein. And in order to clearly describe the present application in the drawings, parts irrelevant to the description are omitted, and similar reference numerals are attached to similar parts throughout the specification.

Throughout this specification, when a part is said to be "connected" to another part, this includes not only the case of being "directly connected" but also the case of being "electrically connected" with another element in between. do.

Throughout the present specification, when a member is referred to as being “on,” “above,” “on top of,” “below,” “below,” or “below” another member, this means that a member is located in relation to another member. This includes not only the case of contact but also the case of another member between the two members.

Throughout the present specification, when a part "includes" a certain component, it means that it may further include other components without excluding other components unless otherwise stated.

As used herein, the terms "about," "substantially," and the like are used at or approximating that number when manufacturing and material tolerances inherent in the stated meaning are given, and are intended to assist in the understanding of this disclosure. Accurate or absolute figures are used to prevent undue exploitation by unscrupulous infringers of the stated disclosure. In addition, throughout the present specification, “steps of” or “steps of” do not mean “steps for”.

Throughout the present specification, the term "combination thereof" included in the expression of the Markush form means one or more mixtures or combinations selected from the group consisting of the components described in the expression of the Markush form, and the components It means including one or more selected from the group consisting of.

Throughout this specification, reference to "A and/or B" means "A, B, or A and B".

Hereinafter, the ultra-thin microneedle electrode of the present application and its manufacturing method will be described in detail with reference to embodiments and examples and drawings. However, the present application is not limited to these embodiments and examples and drawings.

As a technical means for achieving the above technical problem, the first aspect of the present application is a needle-shaped sacrificial layer 100 containing a water-soluble polymer, a support layer 200 formed on the needle-shaped sacrificial layer 100, and an electrode layer 300 formed on the support layer 200 to provide an ultra-thin microneedle electrode 10 .

1 and 2 are schematic diagrams of an ultra-thin microneedle electrode 10 according to an embodiment of the present application, and FIG. 3 is a process of fixing the ultra-thin microneedle electrode 10 according to an embodiment of the present application on a living tissue. At this time, FIG. 1 is a case where there is a flat area at the bottom of the needle-shaped sacrificial layer 100, and FIG. 2 is a case where the needle-shaped sacrificial layer 100 of the ultra-thin microneedle electrode 10 is formed on the substrate 500. it means that

Although described later, referring to FIGS. 1 and 2 , the ultra-thin microneedle electrode 10 according to the present application includes a needle-shaped sacrificial layer 100, a support layer 200 formed on the needle-shaped sacrificial layer 100, It may include an electrode layer 300 formed on the support layer 200, and an adhesive layer 400 formed on the electrode layer 300, wherein the adhesive layer 400 formed on the oblique region of the electrode layer 300 It is omitted from FIGS. 1 and 2 .

According to one embodiment of the present application, the needle-shaped portion of the electrode layer 300 may penetrate the surface of the biological tissue and be fixed on the biological tissue, but is not limited thereto.

According to one embodiment of the present application, after the ultra-thin microneedle electrode 10 is fixed on a living tissue, the needle-shaped sacrificial layer 100 may be removed by moisture supplied from the outside, but is limited thereto It is not.

The needle-shaped sacrificial layer 100 according to the present application serves as a support for maintaining the shape of the electrode layer 300 and hardness for the ultra-thin microneedle electrode 10 to penetrate the surface of living tissue.

The biological tissue may include skin. In this case, when the biological tissue is skin, the surface of the biological tissue may include a stratum corneum, and since the stratum corneum is dead cells, it may function as an insulator. It may interfere with signal measurement. To this end, the height of the needle-shaped sacrificial layer 100 must be secured so that the electrode layer 300 can penetrate the dermal layer or the stratum corneum.

That is, when the ultra-thin microneedle electrode 10 is placed on the surface of the biological tissue so that the electrode layer 300 of the ultra-thin microneedle faces the surface of the biological tissue, the hardness and needle shape of the sacrificial layer cause the The sacrificial layer 100 of the ultra-thin microneedle electrode 10 may penetrate the surface of the biological tissue, and at this time, the ultra-thin microneedle electrode 10 penetrating the surface by the adhesive layer 400 to be described later may penetrate the biological tissue. It can be fixed on tissue. Subsequently, when water is supplied to the ultra-thin microneedle electrode 10, the water-soluble polymer of the ultra-thin microneedle electrode 10 can be dissolved and removed by the water, and the dissolved water-soluble polymer is removed from the surface of the biological tissue. Through this, it can be discharged to the outside of living tissue.

At this time, since the electrode layer 300 for sensing the biosignal and the support layer 200 for maintaining the shape of the electrode layer 300 are formed on the surface of the removed sacrificial layer 100, the moisture Even if the sacrificial layer is removed by the ultra-thin microneedle electrode 10 through the support layer 200 and the electrode layer 300 can detect various biosignals transmitted through biological tissue.

According to one embodiment of the present application, the maximum height of the needle shape may be 50 μm to 1,000 μm, but is not limited thereto. For example, the maximum height of the needle shape is about 50 μm to about 1,000 μm, about 60 μm to about 1,000 μm, about 70 μm to about 1,000 μm, about 80 μm to about 1,000 μm, about 90 μm to about 1,000 μm , about 100 μm to about 1,000 μm, about 200 μm to about 1,000 μm, about 300 μm to about 1,000 μm, about 400 μm to about 1,000 μm, about 500 μm to about 1,000 μm, about 600 μm to about 1,000 μm, about 700 μm to about 1,000 μm, about 800 μm to about 1,000 μm, about 900 μm to about 1,000 μm, about 50 μm to about 60 μm, about 50 μm to about 70 μm, about 50 μm to about 80 μm, about 50 μm to about 90 μm, about 50 μm to about 100 μm, about 50 μm to about 200 μm, about 50 μm to about 300 μm, about 50 μm to about 400 μm, about 50 μm to about 500 μm, about 50 μm to about 600 μm, about 50 μm to about 700 μm, about 50 μm to about 800 μm, about 50 μm to about 900 μm, about 60 μm to about 900 μm, about 70 μm to about 800 μm, about 80 μm to about 700 μm , about 90 μm to about 600 μm, about 100 μm to about 500 μm, about 200 μm to about 400 μm, or about 300 μm.

The height of the needle shape means the depth through which the ultra-thin microneedle electrode 10 penetrates the surface of the biological tissue. In general, since the thickness of the stratum corneum is known to be 50 μm, the maximum height of the needle shape should be greater than 50 μm, but when the electrode layer 300 contacts the dermis layer located below the stratum corneum, it is possible to contact blood vessels or immune cells. Because of this, the maximum height of the needle shape should be less than 1,000 μm, which is the depth to the dermal layer.

According to one embodiment of the present application, the water-soluble polymer is a water-soluble polymer selected from the group consisting of polyvinyl alcohol (PVA), poly acrylic acid (PAA), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), and combinations thereof It may include, but is not limited thereto.

According to one embodiment of the present application, the substrate 500 may include the water-soluble polymer, and in this case, the material of the substrate 500 and the needle-shaped sacrificial layer 100 are matched to form an ultra-thin microneedle electrode. When the substrate 500 and the needle-shaped sacrificial layer 100 are integrated, the structure shown in FIG. 1 may be obtained.

The water-soluble polymer needs to have a hardness of at least a certain level when hardened to the extent that the sacrificial layer penetrates living tissue, and is biocompatible. Specifically, in order for the sacrificial layer to penetrate the living tissue (for example, skin), the mechanical properties of the sacrificial layer are Young's modulus of 1 MPa or more and ultimate tensile strength of 10 Mpa or more. can be satisfied.

At this time, the mechanical properties may vary depending on the shape or shape of the sacrificial layer.

According to one embodiment of the present application, the needle-shaped sacrificial layer 100 may be formed on a water-soluble polymer substrate 500, but is not limited thereto. Specifically, the sacrificial layer may be made of the same material as the substrate 500, and the substrate 500 simultaneously covers an area where the needle-shaped sacrificial layer 100 is formed and a relatively flat area where the sacrificial layer is not formed. can include

According to one embodiment of the present application, the adhesive layer 400 may be formed on the electrode layer 300, but is not limited thereto.

As described above, the electrode layer 300 is formed on the needle-shaped sacrificial layer 100, and at this time, the needle-shaped sacrificial layer 100 is formed on the substrate 500 on which the needle-shaped sacrificial layer 100 is formed. The adhesive layer 400 may also be formed in an area without the needle-shaped sacrificial layer 100 in the ultra-thin microneedle electrode 10 .

In this regard, when the adhesive layer 400 is a material through which electricity flows, that is, a conductive material, it can be formed on the surface of the electrode layer 300 to provide adhesion and simultaneously allow electricity to flow. However, when the adhesive layer 400 is made of a material through which electricity does not flow, when the adhesive layer 400 is formed on the surface of the electrode layer 300, signal measurement of the electrode layer 300 may be hindered. Therefore, the adhesive layer 400 is basically formed on a flat surface of the ultra-thin microneedle electrode 10, and only when the adhesive layer 400 is a conductive material, the adhesive layer 400 is applied to the surface of the electrode layer 300. can be formed

According to one embodiment of the present application, the adhesive layer 400 may include one selected from the group consisting of acrylate, silicone, epoxy, and combinations thereof, but is not limited thereto. no.

According to one embodiment of the present application, the support layer 200 may include a material having biocompatibility, but is not limited thereto.

Although the support layer 200 is located below the electrode layer 300, it needs to have biocompatibility as much as it penetrates the surface of the biological tissue, and has a sufficient modulus so that damage does not easily occur even if the biological tissue moves. and elasticity.

According to one embodiment of the present application, the supporting layer 200 may have CVD compatibility, but is not limited thereto.

As will be described later, the support layer 200 is formed on the needle-shaped sacrificial layer 100, and when formed by the PVD method, the degree of formation of the tarnished layer may be low in an area with a low height. To this end, the support layer 200 may be manufactured by the CVD method and uniformly formed on the needle-shaped sacrificial layer 100 and the substrate 500 on which the sacrificial layer is formed.

According to one embodiment of the present application, the support layer 200 is a parylene polymer (parylene polymer), poly (1,3,5-trivinyl trimethyl cyclotrisiloxane) (poly (1,3,5-trivinyl trimethyl cyclotrisiloxane) )), and those selected from the group consisting of combinations thereof, but are not limited thereto. Specifically, the parylene polymer is parylene N (poly para xylylene), parylene C (dichloro para xylylene), parylene D (tetra chloro xylylene), parylene F (octafluoro-[2,2] para-cyclephane) , parylene AF4 (1,1,2,2,9,9,10,10-Octafluoro[2,2]paracyclophane), and a dimer selected from the group consisting of combinations thereof. However, it is not limited thereto.

In addition to this, the support layer 200 may include polyamide, pPFDA (poly(1H,1H,2H,2Hperfluorodecyl acrylate)), pDVB (poly-(divinylbenzene)), PTFE (Poly(tetrafluoroethylene)), p( GMA) (Poly(glycidyl methacrylate)), p(DMAMS) (Poly(dimethylaminomethyl styrene)), poly(trivinyltrimethoxycyclotrisiloxane), poly(pentapulolophenyl methacrylate -Co-ethylene glycol diacrylate (Poly(pentafluorophenyl methacrylate-co-ethylene glycol diacrylate)), poly(2-hydroxyethyl methacrylate-co-ethylene glycol diacrylate) (Poly(2-hydroxyethyl methacrylate-co-ethylene glycol diacrylate), poly(methacrylic acid-co-ethylene glycol dimethacrylate), PDMAMS (poly[(dimethylaminomethyl)styrene] ), p(NPMA-co-EGDA) (Poly(Neopentyl methacrylate-co-ethylene glycol diacrylate)), pHEMA (Poly(hydroxyethylmethacrylate)), pCHMA (poly(cyclohexylmethacrylate)), and combinations thereof. It may include, but is not limited thereto.

As will be described later, the support layer 200 may be produced by thermal decomposition of a dimer selected from the group consisting of Parylene N, Parylene C, Parylene D, Parylene F, Parylene AF4, and combinations thereof. .

According to one embodiment of the present application, the thickness of the support layer 200 may be 10 nm to 10 μm, but is not limited thereto:

When the thickness of the support layer 200 exceeds 10 μm, mismatch may occur because the electrode layer 300 does not uniformly follow the curves of the biological tissue or grooves between biological tissues such as pores, , it is possible to weaken the adhesive force between the ultra-thin microneedle electrode 10 and living tissue.

According to one embodiment of the present application, the electrode layer 300 is from the group consisting of Au, Cr, Pt, Ag, Fe, Cu, Ni, Ti, graphene, carbon nanotubes, conductive polymers, and combinations thereof. It may include selected ones, but is not limited thereto.

The electrode layer 300 is for collecting bio signals from the ultra-thin microneedle electrode 10 .

According to one embodiment of the present application, the conductive polymer is PEDOT (poly (3,4-ethylene dioxythiophene)), polyaniline (polyaniline), poly (para-phenylene vinylene) (poly (para-phenylene vinylene), poly (para-phenylene) (poly(para-phenylene)), polyacetylene, polypyrrole, polythiophene, poly(p-phenylene sulfide), polyaniline, and combinations thereof It may include those selected from, but is not limited thereto.

According to one embodiment of the present application, the ultra-thin microneedle electrode 10 is an electroencephalogram (EEG), a heart signal (electrocardiogram, ECG), a muscle signal (electromyogram, EMG), the concentration of uric acid, the concentration of lactic acid, glucose Concentration of, components in body fluids, components in saliva, and those selected from the group consisting of combinations thereof may be measured, but is not limited thereto.

According to one embodiment of the present application, the ultra-thin microneedle electrode 10 may further include an external electronic device, but is not limited thereto. At this time, the external electronic device may measure the biosignal collected from the electrode layer 300 and show it on a display or the like.

In addition, the second aspect of the present application is a step of preparing a water-soluble polymer sacrificial layer 100 having a needle shape, forming a support layer 200 on the water-soluble polymer sacrificial layer 100, and the support layer 200 It provides a method of manufacturing an ultra-thin microneedle electrode 10, which includes forming an electrode layer 300 thereon.

Regarding the manufacturing method of the ultra-thin microneedle electrode 10 according to the second aspect of the present application, detailed descriptions of portions overlapping with those of the first aspect of the present application have been omitted. The content can equally apply to the second aspect of the present application.

4 is a flowchart illustrating a method of manufacturing an ultra-thin microneedle electrode 10 according to an exemplary embodiment of the present disclosure.

First, a needle-shaped water-soluble polymer sacrificial layer is prepared (S100).

According to one embodiment of the present application, the step of preparing the sacrificial layer includes preparing a substrate 500 including the water-soluble polymer, and processing the substrate 500 to form a needle shape on the substrate 500. It may include forming a sacrificial layer 100 and a region where the sacrificial layer is not formed, or forming a substrate on which a needle-shaped sacrificial layer 100 is formed through a mold, but is limited thereto. it is not going to be

Preferably, when a mold including a plurality of needle-shaped holes is prepared and a liquefied or gelled water-soluble polymer is supplied to the mold, the needle-shaped sacrificial layer 100 is formed by the holes of the mold. can At this time, when the water-soluble polymer is cured and the mold is removed, the substrate 500 on which the needle-shaped sacrificial layer 100 is formed may be formed.

As described above, the support layer 200 and the electrode layer 300 may be formed on the surface of the needle-shaped sacrificial layer 100, and the adhesive layer 400 may be formed in a region where the sacrificial layer is not formed.

Subsequently, a support layer 200 is formed on the water-soluble polymer sacrificial layer (S200). At this time, the water-soluble polymer sacrificial layer is the same as the needle-shaped sacrificial layer 100 .

According to one embodiment of the present application, the forming of the support layer 200 may be performed by a chemical vapor deposition (CVD) method, but is not limited thereto.

In this regard, when the support layer 200 is parylene, the support layer 200 may be manufactured by a Gorham method. Specifically, in the deposition of the support layer 200, the dimer is vaporized at 150°C to 200°C, and the dimer is pyrolyzed into monomers by passing through a thermal decomposer having an environment of 550°C to 650°C and 0.1 torr to 0.5 torr. It may include the step of being attached to the target surface in a chamber at -40 ° C to 30 ° C, preferably room temperature, and a pressure of 120 mtorr or less to form a parylene polymer, but is limited thereto It is not. In addition, when the support layer 200 is poly(1,3,5-trivinyltrimethylcyclotrisiloxane), it may be deposited by an initiated chemical vapor deposition (iCVD) method, but is not limited thereto.

Subsequently, an electrode layer 300 is formed on the support layer 200 (S300).

According to one embodiment of the present application, the forming of the electrode layer 300 is composed of physical vapor deposition (PVD), sputtering, CVD, atomic layer deposition (ALD), dip coating, spin coating, and combinations thereof. It may be performed by a method including one selected from the group, but is not limited thereto. Specifically, the step of forming the electrode layer 300 includes one selected from the group consisting of thermal evaporation, e-beam evaporation, plasma sputtering, and combinations thereof It can be performed by the PVD method of doing.

In this regard, the sputtering method among the PVD methods can deposit metal isotropically compared to other deposition methods, so the electrode layer 300 can be formed by a plasma sputtering process.

According to one embodiment of the present application, a step of forming an adhesive layer 400 on the electrode layer 300 may be further included, but is not limited thereto.

As described above, the adhesive layer 400 may be formed on a flat portion of the electrode layer 300, and may be formed on all regions of the electrode layer 300 only when the material used as the adhesive layer 400 has conductivity. can

In the forming of the adhesive layer 400, an adhesive material is formed by lithography or screen printing according to the shape of the adhesive layer to be attached to the ultra-thin microneedle electrode 10 on a substrate different from the needle-shaped sacrificial layer 100. A step of forming, and a step of transferring the adhesive material onto the electrode layer 300 may be included, but the present invention is not limited thereto.

The third aspect of the present application is the step of disposing the electrode layer 300 of the ultra-thin microneedle electrode 10 according to the first aspect of the present application on the biological tissue so as to penetrate the biological tissue, the ultra-thin microneedle electrode 10 Providing a biosignal measurement method comprising the steps of supplying moisture to the sacrificial layer 100 to remove the sacrificial layer, and measuring the biosignal through the electrode layer 300 disposed on the skin. do.

With regard to the method for measuring biosignals according to the third aspect of the present application, detailed descriptions of portions overlapping with the first and/or second aspects of the present application have been omitted. Alternatively, the content described in the second aspect may be equally applied to the third aspect of the present application.

As described above, the ultra-thin microneedle electrode 10 is disposed on the biological tissue such that the electrode layer 300 faces the surface of the biological tissue. At this time, since the needle-shaped sacrificial layer 100 has an appropriate hardness, when appropriate pressure is applied from the outside, the needle-shaped sacrificial layer 100 can penetrate the biological tissue, and the ultra-thin microneedle electrode 10 ) can be fixed on the biological tissue by the adhesive layer 400 formed on the non-needle-shaped portion.

Subsequently, when moisture is supplied to the ultra-thin microneedle electrode 10 fixed on the biological tissue, the sacrificial layer 100 containing the water-soluble polymer is removed, and the support layer 200 and the electrode layer 300 not containing the water-soluble polymer are removed. ), and the adhesive layer 400 may be present in a fixed state on the biological tissue. That is, a biosignal generated by or transmitted to the biological tissue can be measured through the electrode layer 300 fixed on the biological tissue.

According to one embodiment of the present application, the biosignal is an electroencephalogram (EEG), a heart signal (electrocardiogram, ECG), a muscle signal (electromyogram, EMG), a concentration of uric acid, a concentration of lactic acid, a concentration of glucose, a body fluid components, components in saliva, and those selected from the group consisting of combinations thereof, but are not limited thereto.

When the ultra-thin microneedle electrode 10 according to the present invention is fixed on a biological tissue, the electrode layer 300 of the ultra-thin microneedle electrode 10 is attached to the surface of the biological tissue to transmit a biosignal to an electrical value such as voltage or current. It acts as a transducer that allows it to be read into. In this regard, in the case of electrophysiology, changes in voltage or current caused by changes in ion channels in nerve tissue can be measured, and three electrodes are used to measure one type of signal. need this That is, the voltage difference between the two electrodes can be read and amplified by an amplifier, and the other electrode can be used as a compensation electrode to remove noise.

Specifically, the ultra-thin microneedle electrodes 10 fixed on the biological tissue may be used in a bundle of three units, or one unit may be divided into three units, but is not limited thereto. In this regard, since the distance between the electrodes and the magnitude of the measured signal tend to be proportional to each other, when measuring the sum of the signals generated from the nerve cells between the electrodes, one ultra-thin microneedle electrode 10 is used as three objects. When divided into units, a signal can be measured smaller than when three ultra-thin microneedle electrodes 10 are combined and used as a unit.

On the other hand, in the case of biophysiological signals, physiological substances to be read change the surface of the electrode layer, and thus electrical characteristics read from the electrode layer, such as resistance or impedance, may increase or decrease. That is, the material of the electrode layer can be appropriately replaced in order to measure a desired physiological signal.

According to one embodiment of the present application, the biological tissue to which the ultra-thin microneedle electrode 10 is attached may be different depending on the measurement target.

For example, when using the ultra-thin microneedle electrode 10 to measure brain waves, the position of the electrode layer can be determined by referring to the international 10-20 system, and when measuring muscle signals (EMG), the measurement is made between two electrodes. The desired muscle bundle can be located, and in the case of an electrocardiogram (ECG), the position of the electrode can be determined by referring to the 12-lead ECG placement.

The above-described problem solving means are merely exemplary and should not be construed as intended to limit the present disclosure. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and detailed description of the invention.

The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present application.

[Example 1]: Formation of ultra-thin microneedle electrodes

A substrate having a microneedle sacrificial layer made of PVA was formed using a mold. Subsequently, a parylene polymer was deposited to a thickness of 1 μm on all 3D surfaces of the microneedles using CVD. Specifically, parylene A dimer is vaporized at 150 ° C to 200 ° C, and the dimer is thermally decomposed into monomers by passing through a thermal decomposer having an environment of 550 ° C to 650 ° C and 0.1 torr to 0.5 torr, and then the monomer is - A parylene polymer layer was formed by being adhered to the target surface in a chamber at 40° C. to 30° C., preferably at room temperature, and at a pressure of 120 mtorr or less.

Subsequently, an electrode layer was formed by coating a Cr/Au alloy to a thickness of 100 nm on the parylene polymer layer, and then an acrylic adhesive layer was transferred on a flat area of the substrate where no microneedles were formed to form an ultra-thin microneedle electrode. was formed.

At this time, the maximum height between the flat region and the Cr/Au alloy is about 600 μm.

5 is a cross-sectional view of an ultra-thin microneedle electrode according to an embodiment of the present application, FIG. 6 is a photograph of a substrate on which an ultra-thin microneedle electrode is formed according to an embodiment of the present application, and FIG. 7 (a) to (c) are This is a photograph of an ultra-thin microneedle electrode according to an embodiment of the present application. At this time, (b) of FIG. 7 is a partial area of (a) enlarged, and (c) is a partial area of (b) enlarged.

[Example 2]: Attachment of ultra-thin microneedle electrodes

The electrode layer of the ultra-thin microneedle electrode according to Example 1 is disposed to face the skin, and the ultra-thin microneedle electrode is attached to the skin on which the ultra-thin microneedle electrode is disposed while applying appropriate pressure, so that the ultra-thin microneedle electrode penetrates the stratum corneum of the skin and the adhesive layer is formed on the skin. It was attached and fixed to the surface. Subsequently, water was passed through the ultra-thin microneedle electrode to remove the PVA sacrificial layer.

[Experimental Example 1]

8 (a) shows skin to which conventional medical electrodes are attached, (b) shows skin to which ultra-thin microneedle electrodes according to the present application are attached, and (c) and (d) show conventional microneedles and skin according to the present application. This is a graph of the impedance between the ultra-thin microneedle electrode and the skin. At this time, the medical electrode means that a wet electrode is placed on the skin on a thick metal plate.

In addition, (a) to (c) of FIG. 9 are photographs with conventional microneedle electrodes attached, and (d) to (f) are photographs with ultra-thin microneedle electrodes according to the present application attached.

Referring to FIG. 8 , conventional medical electrodes can block electricity between the electrode and the skin by the stratum corneum, but the ultra-thin microneedle electrode according to the present invention more sensitively measures biosignals of the skin because the electrode penetrates the stratum corneum. can do. Specifically, compared to conventional medical electrodes, the ultra-thin microneedle electrode has a lower impedance at a lower frequency, and electrical signals such as brain waves, heart, muscles, etc. measurable from the skin are mainly meaningful information in a low frequency band of less than 100 Hz. Since it has, the ultra-thin microneedle electrode can measure biosignals more sensitively than conventional medical electrodes.

In addition, referring to FIG. 9 , the conventional microneedle electrode has low flexibility and stretchability characteristics because the needle portion is not dissolved by water and adheres to human skin while maintaining a hard shape. Specifically, when the conventional microneedle electrode is compressed as shown in (b) of FIG. 9, the electrode cannot follow the curve of the skin, and the adhesive area decreases, such as detaching the adhered part. In this case, it may restrict a person's movement and cause great pain, making it unsuitable for long-term use. In addition, when the skin is stretched as shown in (c) of FIG. 9, a part of the electrode may be detached from the skin as in (b).

However, in the case of the ultra-thin microneedle electrode according to the above embodiment, since the sacrificial layer below the electrode dissolves in water and disappears, only a very thin metal electrode layer portion for measuring signals may remain. That is, as shown in (e) and (f) of FIG. 9 , the ultra-thin microneedle electrode can be flexibly bent and stretched along the curves of the skin even when compressed.

That is, the mechanical properties of the conventional microneedle electrode and the ultra-thin microneedle electrode according to the present application vary depending on whether or not the needle portion (specifically, the sacrificial layer of the ultra-thin microneedle electrode of the present application) survives, and this difference As a result, the flexibility, adhesion, and long-term use convenience of the electrode may change.

[Experimental Example 2]

Figure 10 (a) is a graph measuring EEG using an ultra-thin microneedle electrode according to an embodiment of the present application, and (b) is a graph measuring EMG.

Referring to FIG. 10 , it can be confirmed that the ultra-thin microneedle electrode is suitable for measuring brain electrical signals (EEG) and muscle electrical signals (EMG).

The above description of the present application is for illustrative purposes, and those skilled in the art will understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present application. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form.

The scope of the present application is indicated by the following claims rather than the detailed description above, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts thereof should be construed as being included in the scope of the present application.

10: ultra-thin microneedle electrode
100: needle-shaped sacrificial layer
200: support layer
300: electrode layer
400: adhesive layer
500: substrate

Claims (20)

A needle-shaped sacrificial layer containing a water-soluble polymer;
a support layer formed on the needle-shaped sacrificial layer; and
an electrode layer formed on the support layer;
including,
Ultra-thin microneedle electrodes.
According to claim 1,
The ultra-thin microneedle electrode, wherein the needle-shaped portion of the electrode layer penetrates the surface of the biological tissue and is fixed on the biological tissue.
According to claim 1,
After the ultra-thin microneedle electrode is fixed on a living tissue, the needle-shaped sacrificial layer is removed by moisture supplied from the outside, the ultra-thin microneedle electrode.
According to claim 1,
The water-soluble polymer includes a water-soluble polymer selected from the group consisting of polyvinyl alcohol (PVA), poly acrylic acid (PAA), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), and combinations thereof. electrode.
According to claim 1,
The maximum height of the needle shape is 50 μm to 1,000 μm, ultra-thin microneedle electrode.
According to claim 1,
An adhesive layer is formed on the electrode layer, ultra-thin microneedle electrode.
According to claim 6,
The adhesive layer is an ultra-thin microneedle electrode comprising one selected from the group consisting of acrylate, silicone, epoxy, and combinations thereof.
According to claim 1,
The support layer is to include a material having biocompatibility, ultra-thin microneedle electrode.
According to claim 1,
The support layer has a CVD compatibility, ultra-thin microneedle electrode.
According to claim 1,
The support layer is selected from the group consisting of parylene, poly (1,3,5-trivinyl trimethyl cyclotrisiloxane), and combinations thereof Which is to include, ultra-thin microneedle electrode.
According to claim 1,
The thickness of the support layer is 10 nm to 10 μm, ultra-thin microneedle electrode.
According to claim 1,
The electrode layer is an ultra-thin microneedle electrode comprising one selected from the group consisting of Au, Cr, Pt, Ag, Fe, Cu, Ni, Ti, graphene, carbon nanotubes, conductive polymers, and combinations thereof. .
According to claim 12,
The conductive polymer is PEDOT (poly (3,4-ethylene dioxythiophene)), polyaniline, poly (para-phenylene vinylene), poly (para-phenylene) (poly (para-phenylene)), polyacetylene, polypyrrole, polythiophene, poly(p-phenylene sulfide), polyaniline, and combinations thereof, Ultra-thin microneedle electrodes.
According to claim 1,
The ultra-thin microneedle electrode is an electroencephalogram (EEG), heart signal (electrocardiogram, ECG), muscle signal (electromyogram, EMG), uric acid concentration, lactic acid concentration, glucose concentration, body fluid components, saliva components, And to measure the one selected from the group consisting of combinations thereof, ultra-thin microneedle electrode.
preparing a water-soluble polymer sacrificial layer having a needle shape;
forming a support layer on the water-soluble polymer sacrificial layer; and
forming an electrode layer on the support layer;
Which includes,
Manufacturing method of ultra-thin microneedle electrode.
According to claim 15,
Forming the support layer is a method of manufacturing an ultra-thin microneedle electrode, which is performed by a chemical vapor deposition (CVD) method.
According to claim 15,
Forming the electrode layer is performed by a method including one selected from the group consisting of physical vapor deposition (PVD), sputtering, CVD, atomic layer deposition (ALD), dip coating, spin coating, and combinations thereof That is, a method of manufacturing an ultra-thin microneedle electrode.
According to claim 15,
Further comprising the step of forming an adhesive layer on the electrode layer, the manufacturing method of the ultra-thin microneedle electrode.
disposing the electrode layer of the ultra-thin microneedle electrode according to any one of claims 1 to 14 on the biological tissue so as to penetrate the biological tissue;
removing the sacrificial layer by supplying moisture to the sacrificial layer of the ultra-thin microneedle electrode; and
measuring a biosignal through an electrode layer disposed on the skin;
Which includes,
How to measure vital signs.
According to claim 19,
The biosignal is an electroencephalogram (EEG), a heart signal (electrocardiogram, ECG), a muscle signal (electromyogram, EMG), a concentration of uric acid, a concentration of lactic acid, a concentration of glucose, a component in body fluid, a component in saliva, and these To include one selected from the group consisting of combinations of, a biosignal measurement method.

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