WO2025183493A1 - Self-healing microneedle array and magnetic microneedle interface using same - Google Patents

Abstract

The present disclosure relates to a self-healing microneedle array and a magnetic microneedle interface using same. Specifically, a magnetic microneedle array may be provided, in which magnetic nanoparticles are included in the microneedle array and thus heat is generated by an alternating magnetic field applied from the outside, whereby the microneedles are physically softened or deformed in shape due to the heat generated at the tip portion. In addition, a bio-microneedle bioelectrode having electrical conductivity may be provided by coating the surface of the microneedle array with a conductive polymer, thereby enabling stable transmission of electrochemical signals.

Description

Self-healing microneedle array and magnetic microneedle interface using the same

The present disclosure relates to a self-healing microneedle array and a magnetic microneedle interface using the same.

Microneedle technology is widely used in skin beautification through drug delivery, wound healing, and biosignal recording and stimulation. Conventional microneedles require a certain level of rigidity to penetrate the skin and insert into the body, but they carry the inherent risk of breakage or tissue damage after insertion. To prevent breakage in the body, microneedles must maintain the rigidity necessary for skin penetration while also being flexible enough to adapt to the movement of biological tissue after insertion. This is impossible with the polymers, metals, and ceramics commonly used in conventional microneedles. Furthermore, the size and shape of the microneedle tip significantly impacts its strength and stability. For example, longer microneedles are more prone to bending, and sharper tips provide greater penetration. However, existing processes and materials present limitations in controlling the aforementioned microneedle characteristics, tip size, and shape. Furthermore, because microneedles involve direct contact with and penetration of the skin, they must be manufactured from highly biocompatible materials that do not cause skin irritation or allergic reactions. They must also undergo a thorough sterilization process to prevent infection or inflammation. However, some microneedles can become deformed or damaged when exposed to high temperatures or chemicals, necessitating careful material selection and optimization of sterilization methods.

Most existing microneedle technologies for drug delivery utilize a method that naturally dissolves after insertion. However, this approach limits the ability to control the amount of drug administered over time or to inject it at a desired time. Furthermore, most commercially available products are disposable due to these limitations and hygiene concerns. Microneedle technology is needed to enable sterilization or disinfection for routine use, enabling multiple reuse, while maintaining tip shape and drug loading to maintain penetration.

Microneedles can also be used as bioelectrodes. Bioelectrodes are key components of medical electronic devices used to measure bioelectrical signals, record various biosignals, or electrically stimulate the body to diagnose health conditions and treat diseases. Bioelectrodes can be categorized as wet and dry electrodes, depending on how they are attached to the skin. Wet electrodes utilize gel (electrolyte) to ensure good adhesion to the skin and lower skin impedance, allowing for better signal measurement. However, attaching the electrode requires exfoliating the dead skin cells at the site of the gel (electrolyte), which carries a risk of skin damage. Furthermore, the use of conductive gel can cause skin irritation or allergic reactions, and as the gel dries, the skin's impedance increases, making long-term use difficult. Dry electrodes, developed to address the shortcomings of wet electrodes, do not use gel. Unlike wet electrodes, they offer convenient electrode attachment and address the gel-related issues of wet electrodes. However, since they fundamentally do not use electrolytes, biosignals must be measured in a high-impedance environment. Furthermore, they are sensitive to movement, making signal measurement difficult. Furthermore, they are utilized for pain relief and the treatment of musculoskeletal disorders through electrical stimulation of the skin surface, as well as for heat transfer therapy. However, their efficacy is limited due to the limitations of the skin barrier. This fundamental limitation lies in the skin barrier, requiring microneedle technology capable of penetrating the skin and inserting electrodes.

Therefore, to solve these problems, a microneedle technology is needed that is biocompatible, minimizes damage to the skin when invasive, and can maintain high performance for a long time due to its property of softening due to body temperature after insertion. In addition, a self-recovery microneedle technology that can be sterilized/disinfected after use and maintains penetrability is needed, and in addition, a technology that can release heat from the tip of the microneedle depending on the external environment after insertion, control the amount of drug released, or release it at a desired time is needed.

The present disclosure has been made to solve the problems of the prior art, and provides a magnetic microneedle made of magnetic nanoparticles and a polymer, and a method for manufacturing the same, which can control heat generation and control or maximize drug delivery.

According to another aspect of the present disclosure, a microneedle bioelectrode that does not damage skin tissue when inserted into a body and a method for manufacturing the same can be provided.

According to another aspect of the present disclosure, a self-healing microneedle array that can be restored by heat after use and can be reused, and a bioelectrode using the same can be provided.

According to another aspect of the present disclosure, a method for manufacturing a microneedle array using a 3D printing process to control the angle of a microneedle tip can be provided.

The present disclosure provides a microneedle array comprising: a base portion; and a plurality of microneedles formed to extend outward from one surface of the base portion so as to be inserted into the skin, the microneedles having shapes that are deformed by an external stimulus; wherein the microneedles include a shape memory polymer.

In one embodiment of the present disclosure, the shape memory polymer may be a biocompatible shape memory polymer that is restored according to temperature or infrared irradiation.

In one embodiment of the present disclosure, the shape memory polymer may include at least one selected from the group consisting of 1,3,5-Triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), Trimethylolpropane tris(3-mercaptopropionate) (TMTMP), Tricyclodecane dimethanol diacrylate (TCMDA), 2,2-dimethoxy-2-phenylacetophenone (DMPA), poly(methyl methacrylate), polyurethane, cross-linked polycaprolactone, polysilsesquioxane grafted with polyethylene glycol, and copolymers thereof.

In one embodiment of the present disclosure, the tip of the microneedle may have an asymmetric structure having an inclination of 30 to 60°.

In one embodiment of the present disclosure, the tip of the microneedle includes a tip portion including a magnetic nanoparticle, wherein the magnetic nanoparticle is a nanoparticle of iron oxide including Fe ₂ O ₃ or Fe ₃ O ₄ or a nanoparticle including Fe ₂ O ₃ or Fe ₃ O ₄ . It may be an alloy particle with at least one selected from the group consisting of iron oxide and magnesium (Mg), barium (Ba), manganese (mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr).

In one embodiment of the present disclosure, the tip portion may be heated by an alternating magnetic field applied from the outside of the base portion, and the physical properties of the microneedle may be softened or the shape may be deformed by the heating of the tip portion.

In one embodiment of the present disclosure, a microneedle bioelectrode is provided, which includes a conductive layer including a conductive polymer on the entire surface of the aforementioned microneedle array.

In one embodiment of the present disclosure, the conductive layer may be at least one selected from the group consisting of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS), methanol-treated poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate): polyethylene glycol (methanol doped PEDOT:PSS:PEG200), MXene, and polypyrrole (PPy).

In one embodiment of the present disclosure, the microneedle bioelectrode may be for measuring a biosignal including any one of the group consisting of electrocardiogram, electromyogram, electroencephalogram, and nerve conduction.

In another embodiment of the present disclosure, a method for manufacturing a microneedle array is provided, comprising: (S100) a step of manufacturing a microneedle structure in which a plurality of microneedles are arranged; (S200) a step of forming a microneedle mold by injecting the microneedle structure into a container containing a first polymer material; and (S300) a step of forming a microneedle array by injecting a shape memory polymer into the microneedle mold.

In one embodiment of the present disclosure, the microneedle structure comprises a substrate portion and a plurality of microneedles protruding from the base portion, and in the step of manufacturing the microneedle structure (S100), the microneedle structure may be manufactured using 3D printing, and the base portion may be arranged at a predetermined angle of inclination with respect to the stage of the 3D printer.

In one embodiment of the present disclosure, the base portion of the microneedle structure may be arranged at an inclination angle of 30 to 60° relative to the stage of a 3D printer.

In one embodiment of the present disclosure, in the step (S300), magnetic nanoparticles are further injected into the negative mold, and the step (S300) may include a vacuum placement step in which a mold into which a mixture of a shape memory polymer and magnetic nanoparticles is injected is placed in a vacuum; a magnet placement step in which a magnet is placed on the outside of a microneedle mold placed in a vacuum in the vacuum placement step; and a self-assembly step in which the shape memory polymer and magnetic nanoparticles injected into the microneedle mold in which the magnet is placed in the magnet placement step are separated and self-assembled.

In one embodiment of the present disclosure, the magnetic nanoparticles are nanoparticles of iron oxide including Fe ₂ O ₃ or Fe ₃ O ₄ or nanoparticles of iron oxide including Fe ₂ O ₃ or Fe ₃ O _4. It may be an alloy particle with at least one selected from the group consisting of iron oxide and magnesium (Mg), barium (Ba), manganese (Mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr).

In one embodiment of the present disclosure, the size of the magnetic nanoparticles may be 5 nm to 500 μm.

In one embodiment of the present disclosure, a microneedle array manufactured according to the manufacturing method described above is provided, wherein the microneedle tips of the microneedle array may have an asymmetric structure having an inclination of 30 to 60°.

In one embodiment of the present disclosure, a skin invasive device that stimulates the skin by invading the skin using magnetic microneedles is provided, the skin invasive device comprising: a magnetic microneedle array including a plurality of microneedles that are invasive into the skin; a depth control unit that fixes the plurality of microneedle arrays to control the depth of penetration into the skin; a substrate unit having a plurality of holes formed therein so that the plurality of microneedles can pass through and infiltrate the skin; a magnetic field generating unit provided on the outside of the substrate unit to generate a magnetic field; and a tip unit containing magnetic nanoparticles that generate heat by the magnetic field generating unit.

In one embodiment of the present disclosure, a method for manufacturing a microneedle bioelectrode is provided, comprising: a step of manufacturing a microneedle array according to the above-described manufacturing method; and (S400) a step of separating the microneedle array from the microneedle mold to form a conductive layer including a conductive polymer on the surface of the microneedle array.

In one embodiment of the present disclosure, the microneedle array forming step (S300) may include a shape memory polymer injection step (S310) into a microneedle mold; a vacuum placement step (S320); and a microneedle array curing step (S350).

In one embodiment of the present disclosure, immediately after separating the microneedle array in step (S400), the method may further include a step of activating the shape memory polymer surface by treating the shape memory polymer surface with at least one plasma selected from the group consisting of O ₂ , Ar, and N ₂ .

In one embodiment of the present disclosure, the conductive polymer may be at least one selected from the group consisting of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS), methanol-treated poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate): polyethylene glycol (methanol doped PEDOT:PSS:PEG200), MXene, and polypyrrole (PPy).

In one embodiment of the present disclosure, a microneedle bioelectrode manufactured according to the above-described microneedle bioelectrode manufacturing method is provided.

According to the present disclosure, by forming magnetic nanoparticles inside the tip of microneedles formed of a shape memory polymer, the temperature of the tip can be increased by an external magnetic field, thereby inducing a shape memory effect of the shape memory polymer microneedles, thereby allowing the shape of the microneedles to be continuously maintained.

Additionally, the amount of drug delivery can be controlled or maximized by controlling heat generation according to the magnetic field strength.

In addition, it can be used in conjunction with an extracorporeal magnetic field therapy device to generate heat through magnetic nanoparticles generated by the extracorporeal magnetic field, enabling thermal therapy, so it can be used in various medical fields such as moxibustion, drug delivery, thermal therapy devices, thermal vascular stents, and bioelectrodes.

Additionally, the magnetic material located at the tip can maximize the magnetic field stimulation by focusing the magnetic field applied from the outside.

According to one embodiment of the present disclosure, a bioelectrode and a method for manufacturing the same include a shape memory polymer in the needle portion of a microneedle array, so that the needle portion is hard before insertion into the body and can puncture the skin, and after insertion, it becomes flexible due to body temperature and can avoid damaging living tissue even when the body moves.

In addition, by molding the shape and angle of the microneedle tip to maximize penetration power by producing a microneedle with a finely adjusted microneedle tip output through a 3D printing process, a microneedle bioelectrode with high skin perforation performance can be manufactured.

A bioelectrode and a method for manufacturing the same according to one embodiment of the present disclosure can be restored by heat or infrared irradiation after use and reused, and even after reuse, the shape and performance are restored to the initial state so that the bioelectrode can be utilized for its original function.

According to one embodiment of the present disclosure, a bioelectrode and a method for manufacturing the same have an elasticity such that the base of the microneedle bioelectrode can be flexibly stretched, so that after being attached to the skin, the electrode does not fall off from the skin or become damaged even when the body moves.

A bioelectrode and a method for manufacturing the same according to one embodiment of the present disclosure can detect a nerve signal by connecting to an external measuring device or an external stimulator or transmit an electrical stimulus to a nerve as an interface.

Figure 1 is a schematic diagram of a magnetic microneedle array of the present disclosure.

Figure 2 illustrates a flow chart of a method for manufacturing a magnetic microneedle array of the present disclosure.

Figure 3 is a schematic diagram illustrating a method for manufacturing a magnetic microneedle array of the present disclosure.

FIG. 4 illustrates a flow chart of the magnetic microneedle array formation steps of the magnetic microneedle array manufacturing method of the present disclosure.

Figure 5 is a schematic diagram illustrating a magnetic microneedle array formation step of the magnetic microneedle array manufacturing method of the present disclosure.

FIG. 6 is a schematic diagram illustrating an invasive method of a skin invasive device that is manufactured using a magnetic microneedle array of the present disclosure to invasively stimulate the skin.

Figure 7 illustrates a schematic diagram of the operation of a magnetic microneedle array when a magnetic field is applied from an external source.

Figure 8 shows a graph showing the results of the heating characteristics of magnetic nanoparticles of the magnetic microneedle of the present disclosure.

Figure 9 shows a graph showing the results of the heating characteristics of the magnetic microneedles of the present disclosure.

Figure 10 illustrates thermal imaging camera results demonstrating shape memory capability using the heating characteristics of the magnetic microneedles of the present disclosure.

Figure 11 is a schematic diagram of a microneedle bioelectrode according to one embodiment of the present disclosure.

Figure 12 is a schematic diagram of a method for manufacturing a microneedle bioelectrode of the present disclosure.

Figure 13 shows the inclination angle of the base portion with respect to the stage of a 3D printer during the microneedle structure manufacturing step.

Figure 14 illustrates the tip portion of a microneedle according to the inclination angle in the microneedle structure manufacturing step.

FIG. 15 illustrates a drawing of a microneedle bioelectrode of Example 3 of the present disclosure.

Figure 16 is a graph showing the durability of the microneedle bioelectrode of Example 3 of the present disclosure.

Figure 17 illustrates the form of the microneedle bioelectrode of Example 3 of the present disclosure before being inserted into the body.

Figure 18 illustrates the appearance of the microneedle bioelectrode of Example 3 of the present disclosure after 50 uses.

Figure 19 illustrates the appearance of a microneedle bioelectrode of the present disclosure after being heated and recovered after being used 50 times.

Figure 20 (a) illustrates a microneedle bioelectrode attached to a patient with a lower extremity amputation, (b) illustrates a photograph of the microneedle bioelectrode removed after 6 hours of wearing it, and (c) illustrates the microneedle bioelectrode worn together with a robotic prosthesis using a wireless electromyography signal recording system.

Figure 21 shows the signal-to-noise ratio (SNR) measured in a treadmill exercise situation.

Figure 22 is a graph showing the frequency analysis results of an electromyography signal measured with a fabricated microneedle bioelectrode (Example 3) and the frequency analysis results of an electromyography signal measured with a currently commercially available surface electrode (Comparative Example 1).

Figure 23 illustrates an electromyography signal in a kicking situation after wearing the microneedle bioelectrode and surface electrode of Example 3 of the present disclosure.

Figure 24 (a) shows the surface resistance measured after 50 uses of the microneedle bioelectrode of Example 3 of the present disclosure and the surface resistance measured after recovery, and Figure 24 (b) shows the surface resistance measured after surface cutting and the surface resistance measured after recovery.

Figure 25 is a graph showing the durability test results of Example 3 and Comparative Example 2 of the present disclosure.

The advantages and features of the present disclosure, and methods for achieving them, will become clearer with reference to the embodiments described in detail below. However, the present disclosure is not limited to the embodiments disclosed below and may be implemented in various different forms. These embodiments are provided solely to ensure the complete disclosure of the present disclosure and to fully inform those skilled in the art of the present disclosure of the scope of the invention. The present disclosure is defined solely by the scope of the claims.

Unless otherwise defined, all terms (including technical and scientific terms) used in this specification may be used in a meaning that can be commonly understood by a person of ordinary skill in the art to which this disclosure belongs.

As used herein, the singular forms of terms may be construed to include the plural forms as well, unless otherwise specified.

The numerical ranges used herein include lower and upper limits and all values within that range, increments logically derived from the shape and width of the defined range, all doubly defined values, and all possible combinations of upper and lower limits of numerical ranges defined in different shapes. Unless otherwise specified in the specification of the present disclosure, values outside the defined range that may arise due to experimental error or rounding of values are also included in the defined numerical range.

The term "includes" as used herein is an open-ended description having the equivalent meaning of expressions such as "comprises," "contains," "has," and "characterizes," and does not exclude additional elements, materials, or processes not listed.

The 'microneedle tip' referred to in this specification means the terminal portion of the microneedle that first comes into contact with the skin when inserted into the skin.

The 'aspect ratio' referred to in this specification means the ratio of the height to the base of the microneedle.

Below, the self-healing microneedle array and magnetic microneedle interface of the present disclosure will be described in detail. However, these are merely exemplary and the present disclosure is not limited to the specific embodiments described as examples.

The present disclosure provides a microneedle array comprising: a base portion; and a plurality of microneedles formed to extend outward from one surface of the base portion so as to be inserted into the skin, the microneedles having shapes that are deformed by an external stimulus; wherein the microneedles include a shape memory polymer.

The above shape memory polymer may include a biocompatible shape memory polymer that does not cause irritation or allergic reaction to the skin and does not cause side effects in the human body, and when manufacturing a microneedle bioelectrode, the material properties of the shape memory polymer may be set according to the type of UV light, exposure time, and temperature and time of hard baking.

According to the above characteristics, it is hard before insertion and can be easily inserted into the body by perforating the skin with little force, and after insertion, the shape memory polymer becomes soft due to the heat of the human body, so tissue damage may not occur even with body movement.

Therefore, the microneedle array of the present disclosure can improve the problems of existing microneedle arrays, such as the risk of microneedles breaking or damaging body tissues after insertion, by including shape memory polymers in the microneedles.

In one embodiment of the present disclosure, the shape memory polymer may be a biocompatible shape memory polymer that is restored according to temperature or infrared irradiation.

The microneedle array of the present disclosure includes a shape memory polymer, thereby providing the microneedle itself with shape memory capabilities, enabling restoration when the shape is bent or damaged by a temperature above a certain level. After use, the microneedle array can be restored to its initial state by undergoing a restoration process through heating or infrared irradiation. Accordingly, the present disclosure provides a microneedle array that can exhibit the same performance as the initial microneedle array even after being inserted into the body 50 or more times and then reused by recovering through heat.

In one embodiment of the present disclosure, the shape memory polymer may include at least one selected from the group consisting of 1,3,5-Triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), Trimethylolpropane tris(3-mercaptopropionate) (TMTMP), Tricyclodecane dimethanol diacrylate (TCMDA), 2,2-dimethoxy-2-phenylacetophenone (DMPA), poly(methyl methacrylate), polyurethane, cross-linked polycaprolactone, polysilsesquioxane grafted with polyethylene glycol, and copolymers thereof.

Specifically, it may be a shape memory polymer composed of 1,3,5-Triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), Trimethylolpropane tris(3-mercaptopropionate) (TMTMP), Tricyclodecane dimethanol diacrylate (TCMDA), and 2,2-dimethoxy-2-phenylacetophenone (DMPA). More specifically, it may be a shape memory polymer composed of 1,3,5-Triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO) 27.630%, Trimethylolpropane tris(3-mercaptopropionate) (TMTMP) 42.642%, Tricyclodecane dimethanol diacrylate (TCMDA) 29.644%, and 2,2-dimethoxy-2-phenylacetophenone (DMPA) 0.083%. However, it is not necessarily limited thereto, and any shape memory polymer that returns to its initial state from temporary deformation due to heat or light stimulation may be used without limitation.

In one embodiment of the present disclosure, the aspect ratio of the microneedle may be 2:1 to 10:1. Specifically, it may be 2:1 to 5:1, and more specifically, it may be 2.5:1 to 3.5:1. However, a person skilled in the art can appropriately design it according to the intended use, and it is not necessarily limited to the above range.

In one embodiment of the present disclosure, the tip of the microneedle may have an asymmetrical structure with an inclination of 30 to 60°. More specifically, when the tip of the microneedle has an inclination of 45 to 55°, the tip is formed sharply, allowing it to pierce the skin painlessly when attached.

In one embodiment of the present disclosure, the tip of the microneedle includes a tip portion including a magnetic nanoparticle, wherein the magnetic nanoparticle is a nanoparticle of iron oxide including Fe ₂ O ₃ or Fe ₃ O ₄ or a nanoparticle including Fe ₂ O ₃ or Fe ₃ O ₄ . A microneedle array can be provided, which is an alloy particle of iron oxide and at least one selected from the group consisting of magnesium (Mg), barium (Ba), manganese (mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr).

Hereinafter, a magnetic microneedle array refers to a microneedle array including a tip portion containing magnetic nanoparticles.

Fig. 1 is a schematic diagram of a magnetic microneedle array of the present invention. In addition, Fig. 1(a) is a schematic diagram of a magnetic microneedle array when no external magnetic field is applied, and Fig. 1(b) is a schematic diagram of a magnetic microneedle array when an external magnetic field is applied. Referring to Fig. 1(a), the magnetic microneedle array of the present invention may include a plurality of microneedles including a base portion, a body portion that extends outward from one surface of the base portion so as to be inserted into the skin and whose shape is deformed by an external stimulus, and a tip portion provided at the end of the body portion. The body portion may include a shape memory polymer. Shape memory polymers can implement a desired shape according to temperature changes, and have the characteristic of becoming softer as the temperature increases. Therefore, by manufacturing such a shape memory polymer as the body portion of the microneedle array, the flexibility and rigidity of the microneedles can be maximized.

In addition, the tip can be formed of magnetic nanoparticles, and in detail, the magnetic nanoparticles are nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O ₄ or nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O _4. It may include alloy particles of iron oxide and at least one selected from the group consisting of magnesium (Mg), barium (Ba), manganese (mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr). In this case, the magnetic nanoparticles have the characteristic of generating heat when a magnetic field is applied.

Therefore, as shown in Fig. 1(b), in the present invention, the body of the microneedle structure may include a shape memory polymer, and the tip may include magnetic nanoparticles. The tip is heated by an alternating magnetic field applied from the outside of the base, and the shape of the body may be deformed due to the heat generated by the tip. As the tip is heated by the alternating magnetic field, the shape memory polymer of the body is flexibly changed, enabling the implementation and restoration of a desired shape. In addition, the tip is capable of additional heat treatment by the magnetic nanoparticles that are heated by the application of the alternating magnetic field.

The tip of the magnetic microarray may be heated by an alternating magnetic field applied from the outside of the base, and the physical properties of the microneedles may be softened or their shape may be deformed by the heating of the tip.

Hereinafter, a microneedle bioelectrode including the above microneedle array will be described in detail.

In one embodiment of the present disclosure, a microneedle bioelectrode can be provided, which includes a conductive layer including a conductive polymer on the entire surface of the above-described microneedle array.

That is, the present disclosure can provide a microneedle bioelectrode including a microneedle array including a base portion and a plurality of microneedles protruding from the base portion; and a conductive layer including a conductive polymer on the entire surface of the microneedle array, wherein the microneedle array includes a shape memory polymer.

Conventional bioelectrodes using metal electrodes often break during use due to the lack of flexibility in the metal substrate, and patients with lower limb amputations often complain of a foreign body sensation or discomfort when attaching the substrate to their body. In contrast, the microneedle bioelectrode of the present disclosure uses a conductive polymer coated on the entire surface, which is easy to process, inexpensive, and highly flexible, instead of a metal electrode, thereby preventing a foreign body sensation or discomfort even when attached to the inside of a prosthetic leg socket.

Therefore, the microneedle bioelectrode of the present disclosure can improve the problems of existing bioelectrodes, such as the risk of microneedles breaking or damaging body tissues in the body after insertion, by including a shape memory polymer in the microneedle array.

Additionally, the present disclosure can provide a bioelectrode having durability and electrical conductivity that can stably transmit electrochemical signals within the body.

After the above microneedle bioelectrode is used, if it undergoes a restoration process by heating or infrared irradiation, the electrode's performance can be restored to its initial state. Therefore, the present disclosure provides a microneedle bioelectrode that can be reused after being inserted into the body 50 or more times and then restored by heat, thereby maintaining the same performance as the initial electrode.

Figure 11 is a schematic diagram of the microneedle bioelectrode of the present disclosure. Referring to Figure 11, it can be seen that the entire surface of the microneedle array, including the shape memory polymer, is coated with a conductive polymer. By coating the surface with the conductive polymer to form a conductive layer, the microneedle can be utilized as a bioelectrode without a separate metal electrode.

The above microneedle bioelectrode is a microneedle-shaped electrode that penetrates the skin with minimal invasion to measure biosignals, thereby being less affected by noise such as body movement, and thus can detect more accurate biosignals and bioresistance.

In one embodiment of the present disclosure, the thickness of the base portion of the microneedle bioelectrode may be 10 to 1000 um. Specifically, it may be 50 to 700 um, and more specifically, it may be 50 to 500 um. More specifically, when the thickness is 250 um, when the microneedle bioelectrode of the present disclosure is attached to a patient undergoing lower leg or femoral amputation, the patient may not feel discomfort inside the socket. However, the thickness of the base portion is not necessarily limited thereto, and a person skilled in the art may appropriately design and use it depending on the position where the microneedle bioelectrode is inserted, the intended use, etc.

The conductive layer may be at least one selected from the group consisting of PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)), PEDOT:PSS:PEG (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate):polyethyleneglycol), Mxene, and polypyrrole (PPy). More specifically, it may be PEDOT:PSS:PEG (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate):polyethyleneglycol), and even more specifically, it may be methanol-treated PEDOT:PSS:PEG (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate):polyethyleneglycol). However, it is not necessarily limited thereto, and a person skilled in the art can appropriately select and use any conductive polymer that can be recovered by heat.

In PEDOT:PSS:PEG, the molecular weight of PEG can be from 100 to 1000, specifically from 200 to 800, and more specifically from 200 to 400.

The concentration of PEG can be controlled within 10%, more specifically within 8%, within 5%, and even more specifically within 4%. When PEG with a molecular weight of 200 or 400 is added to PEDOT:PSS, the shape memory polymer can exhibit an effect of being restored by heat or water even if damaged by deformation.

In addition, when microneedles coated with PEDOT:PSS or PEDOT:PSS:PEG are immersed in alcohol solvents such as methanol or ethanol with a low boiling point, the electrical conductivity can be effectively increased. In addition, the methanol-treated PEDOT:PSS:PEG used in the examples of the present disclosure has a property of being restored by heat or water even if damaged by deformation of the shape memory polymer, and thus can prevent defects in the conductive layer caused by physical deformation of the shape memory polymer. Therefore, even if the deformed microneedle bioelectrode is bent or cracks occur in the conductive layer due to shape change during use, the shape and performance are restored after a certain period of time or when immersed in water above 40°C, so that a high-performance bioelectrode can be provided even when the microneedle is reused.

In one embodiment of the present disclosure, the microneedle bioelectrode may be for measuring a biosignal including any one of the group consisting of electrocardiogram, electromyogram, electroencephalogram, and nerve conduction.

The above microneedle bioelectrode can be manufactured as a microneedle bioelectrode that is easy to insert and attach to the skin by combining it with a silicone liner, and can be used as a sensor-attached silicone liner or exoskeleton robot band that can be used for a long time by combining it with the band part of an exoskeleton robot.

In one embodiment of the present disclosure, a system for detecting and stimulating neural signals can be provided, including the microneedle bioelectrode, an external measuring device, and a connector connectable to the external measuring device.

Hereinafter, the manufacturing method of the microneedle array of the present disclosure will be described in detail.

In another embodiment of the present disclosure, a step of manufacturing a microneedle structure is provided, wherein a structure in which microneedles are arranged in a plurality of rows is manufactured;

A step of forming a microneedle mold by introducing the microneedle structure into a container containing a first polymer material; and

A method for manufacturing a microneedle array can be provided, comprising: forming a microneedle array including a shape memory polymer;

First, the step of manufacturing a microneedle structure (S100) and the step of manufacturing a microneedle mold (S200) will be described in detail.

Conventional microneedle manufacturing technologies have limited the shapes of simple microneedles due to process limitations. However, by using 3D printing technology to manufacture microneedle structures and negative molds, it is possible to design needle shapes with more diverse and complex structures than before. Manufacturing microneedle molds using 3D printing has the advantage of allowing free design of the length of the microneedle structure, the thickness of the base, and other factors depending on the bioelectrode attachment site and intended use.

However, the method for manufacturing the microneedle structure may be manufactured using a 3D printing process, but is not necessarily limited thereto, and may also be manufactured using a conventional molding process. A method for manufacturing a microneedle structure including a base portion and a plurality of microneedles protruding from the base portion may be manufactured using various known methods.

In the microneedle structure manufacturing step (S100), the microneedle structure includes a base portion and a plurality of microneedles protruding from the base portion.

In one embodiment of the present disclosure, in the microneedle structure manufacturing step (S100), the base portion may be positioned at a certain inclination angle with respect to the stage of the 3D printer.

Fig. 13 illustrates the inclination angle of the base portion relative to the stage of a 3D printer in the microneedle structure manufacturing step (S100). Specifically, referring to Fig. 13, the microneedle structure may be configured to include a base portion and a plurality of microneedles protruding from the base portion, and the base portion may be arranged at an inclination angle of 30 to 60° relative to the stage of the 3D printer. More specifically, the base portion may be manufactured as an asymmetric structure having an inclination angle of 45 to 55° relative to the stage of the 3D printer.

Figure 14 illustrates the tip portion of the microneedle according to the inclination angle. Referring to Figure 14, when the inclination angle is 0 or 90°, it can be seen that the tip is blunt rather than sharp. In this case, it is difficult to puncture the skin. As the inclination angle of the base portion increases from 30 to 60° on the stage, the tip becomes sharp, and a phenomenon of the tip shape bending occurs from 60° or more. When the inclination angle is 90°, the tip portion of the microneedle structure is formed bluntly, and when the inclination angle is 45°, the microneedle structure can be formed sharply.

Microneedles are extremely small, measured in microns, and the low resolution of commercial and general-purpose 3D printers has limited the ability to produce precise microneedle arrays. To address this issue, the present disclosure provides a method for producing microneedles with durability and penetrability at the microneedle tip by positioning the base portion at a predetermined angle relative to the stage, thereby controlling the inclination angle of the microneedles to 30 to 60°.

A microneedle mold can be formed by introducing a microneedle structure including the sharp tip portion into a container containing a first polymer material. By manufacturing the microneedle mold having the same negative shape as the microneedle structure, the shape of the microneedle array can be precisely manufactured.

Next, the microneedle mold formation step (S200) will be described.

The microneedle mold forming step (S200) is a step of forming a microneedle mold by injecting the microneedle structure produced in the microneedle structure production step (S100) into a container containing the first polymer material.

The first polymer material may be at least one selected from the group consisting of silicone-based polymers or polyurethane. More specifically, the first polymer material may be polydimethylsiloxane (PDMS), but is not necessarily limited thereto.

In the microneedle mold forming step (S200), a microneedle mold having the same negative shape as the microstructure is manufactured so that the shape of the microneedle array can be manufactured more precisely.

Next, the microneedle array formation step (S300) will be described in detail.

The above microneedle array formation step may include a shape memory polymer injection step (S310), a vacuum placement step (S320), and a microneedle array curing step (S350).

Specifically, after injecting a shape memory polymer into a microneedle engraving mold, the method may further include placing the mold into which the shape memory polymer has been injected in a vacuum. More specifically, the mold may be placed in a vacuum for about 20 minutes to 1 hour. Placing the mold in a vacuum is intended to ensure that no air bubbles exist on the mold surface and to completely inject the shape memory polymer to the ends of the mold to reproduce the microneedle shape.

In one embodiment of the present disclosure, the curing step (S350) of the microneedle array may include a UV curing or hard bake step.

Specifically, it may include primary curing in which the shape memory polymer is cured by exposure to ultraviolet rays, and secondary curing in which the shape memory polymer is cured by being placed in an oven. Accordingly, the shape memory polymer can be completely cured through the primary and secondary curing processes, and the shape memory properties of the shape memory polymer can be designed depending on the ultraviolet irradiation time, exposure time, and hard baking temperature and time.

Next, a method for manufacturing a microneedle array containing magnetic nanoparticles will be described in detail.

For example, in the microneedle array forming step (S300) of the above-described method for manufacturing a microneedle array, a mixture of a formation memory polymer and magnetic nanoparticles may be injected into a mold.

Accordingly, a method for manufacturing a microneedle array can be provided, wherein the microneedle array forming step (S300) includes a vacuum placement step in which a mold into which a mixture of the shape memory polymer and the magnetic nanoparticle is injected is placed in a vacuum; a magnet placement step in which a magnet is placed on the outside of the microneedle mold placed in a vacuum in the vacuum placement step; and a self-assembly step in which the shape memory polymer and the magnetic nanoparticle injected into the microneedle mold in which the magnet is placed in the magnet placement step are separated and self-assembled.

Specifically, the magnetic microneedle array forming step (S300) is a step of forming a magnetic microneedle array by injecting a mixture of shape memory polymers and magnetic nanoparticles into a microneedle mold and curing the mixture. Here, the magnetic microneedle array forming step further includes a mixture injection step (S310), a vacuum placement step (S320), a magnet placement step (S330), a self-assembly step (S340), a curing step (S350), and a microneedle array manufacturing step (S360).

Fig. 4 is a flowchart illustrating a magnetic microneedle array formation step of a method for manufacturing a magnetic microneedle array of the present invention, and Fig. 5 is a schematic diagram illustrating a magnetic microneedle array formation step of a method for manufacturing a magnetic microneedle array of the present invention. The magnetic microneedle array formation step (S300), which further includes a mixture injection step (S310), a vacuum placement step (S320), a magnet placement step (S330), a magnetic assembly step (S340), a curing step (S350), and a microneedle array manufacturing step (S360), will be described in more detail below with reference to Figs. 4 and 5.

The mixture injection step (S310) is a step in which a mixture of shape memory polymers and magnetic nanoparticles is injected into a microneedle mold in which a groove having the same negative shape as the magnetic microneedle structure is formed, as shown in Fig. 5(a).

For example, the magnetic nanoparticles are nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O ₄ or nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O _4. It may be an alloy particle of at least one selected from the group consisting of iron oxide and magnesium (Mg), barium (Ba), manganese (Mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr), but is not necessarily limited thereto.

The above magnetic nanoparticles can range in size from 5 nm to 500 μm. Therefore, a mixture can be manufactured by mixing shape memory polymers and magnetic nanoparticles. At this time, the type, size, and amount of magnetic nanoparticles added can vary depending on the frequency and strength of the externally applied magnetic field.

The above vacuum placement step (S320) is a step in which a mold into which a mixture including a shape memory polymer and magnetic nanoparticles is injected is placed in a vacuum, as shown in Fig. 5(b). Specifically, the microneedle mold into which the mixture of the shape memory polymer and the magnetic nanoparticles is injected is placed in a vacuum for approximately 30 minutes, so that the mixture can easily fill the ends of the mold without external pressure. Accordingly, it is possible to manufacture magnetic microneedles having the same shape as the structure of the microneedle.

The magnet arrangement step (S330) is a step of arranging magnets on the outside of a microneedle mold arranged in a vacuum, as shown in Fig. 5(c). By arranging magnets on the outside of the microneedle mold, the second polymer and magnetic nanoparticles injected into the microneedle mold, where the magnets are arranged in the magnet arrangement step, can be separated and aggregated in the self-assembly step (S340). Accordingly, the magnets are arranged on the outside of the microneedle mold, and thus, the magnetic nanoparticles can be concentrated at the tips of the microneedles.

The above-mentioned hardening step (S350) is a step in which the shape memory polymer and magnetic nanoparticles that were self-assembled and separated inside the self-assembled microneedle mold in the self-assembly step are hardened, as shown in FIG. 5(d) and FIG. 5(e).

At this time, the microneedle array curing step may include primary curing by UV irradiation as shown in Fig. 5d, and secondary curing by being placed in an oven as shown in Fig. 5(e). Primary curing is irradiated with UV for 30 minutes, and secondary curing can be performed in a vacuum oven at 120°C for 24 hours under vacuum. Therefore, the micro array inside the microneedle mold can be completely cured through primary and secondary curing.

The microneedle array manufacturing step (S360) is a step of manufacturing a magnetic microneedle array by separating the hardened magnetic microneedle array from the hardened microneedle mold in the microneedle array hardening step, as shown in Fig. 5(f). Therefore, the hardened microarray by the hardening step (S350) is completely separated from the microneedle mold, and a microneedle array having the same shape as the microneedle mold is manufactured, and the manufactured microarray may include a substrate portion, a body portion formed of a shape memory polymer, and a tip portion containing magnetic nanoparticles, as shown in Fig. 5(f).

A skin invasive device that stimulates the skin by invading the skin using a microneedle array (hereinafter, referred to as a magnetic microneedle array) containing magnetic nanoparticles of the present disclosure comprises a magnetic microneedle array, a depth control unit, a substrate unit, a magnetic field generation unit, and an electric signal unit. Fig. 6 is a schematic diagram of an invasive method of a skin invasive device that stimulates the skin by invading the skin using the magnetic microneedles of the present disclosure. Referring to Fig. 6, a skin invasive device that stimulates the skin by invading the skin using the magnetic microneedles of the present disclosure will be described in detail.

A magnetic microneedle array is configured to include a plurality of microneedles that are invasive into the skin. Specifically, referring to FIG. 6 (a), the magnetic microneedle array is configured to include a plurality of microneedles, including a base portion, a body portion that extends outward from one surface of the base portion so as to be inserted into the skin and whose shape is deformed by an external stimulus, and a tip portion containing magnetic nanoparticles provided at the end of the body portion. In addition, the magnetic microneedle array of the present disclosure comprises a body portion of a microneedle structure made of a shape memory polymer and a tip portion containing magnetic nanoparticles. Accordingly, the tip portion is heated by an alternating magnetic field applied from the outside of the base portion, and the physical characteristics of the body portion may be softened or the shape may be deformed by the heat generated by the tip portion.

The depth control unit can control the depth at which the plurality of microneedle arrays are penetrated into the skin by fixing them. At this time, the depth at which the plurality of microneedles are penetrated into the skin by the depth control unit may be 0.1 mm to 10 mm, but is not necessarily limited thereto, and the depth can be set depending on the penetration site.

Referring to Fig. 6 (b), the skin is composed of the stratum corneum covering the surface of the skin, the epidermis located below the stratum corneum, the dermis, and the subcutaneous tissue. The magnetic microneedle array of the present disclosure is inserted into the dermis, and the tip of the magnetic microneedle is inserted into the dermis. At this time, the tip containing the magnetic nanoparticle can provide thermal stimulation to the skin invasion site or focus the magnetic flux by the magnetic field depending on the frequency and intensity of the alternating magnetic field applied from the magnetic field generating unit. Referring to Fig. 6, when a magnetic field is applied from the outside, the temperature of the tip of the microneedle increases as shown in Fig. 6 (c) and Fig. 6 (d), and the body part composed of the shape memory polymer is deformed in shape due to the increase in temperature, and accordingly, the shape of the tip of the microneedle can also be deformed. Therefore, when a microneedle is inserted into the skin, there is a possibility that the epidermis may be damaged by strong movement or pressure. However, by intentionally applying heat to the tip of the microneedle where the magnetic nanoparticle of the present invention is located, the shape can be gently changed, thereby minimizing the irritation applied to the skin during insertion.

Figure 7 is a schematic diagram of the operation of a magnetic microneedle array when a magnetic field is applied from the outside. Referring to Figure 7, as shown in Figure 7(a), when a magnetic field is applied to the outside of the microneedle array, the tip of the microneedle is heated, which can induce nerve stimulation by heat. In addition, as shown in Figure 7(b), the drug-coated area of the tip may melt due to heat, or the particles inside may melt, allowing the drug to penetrate the skin. In addition, as shown in Figure 7(c), since heat therapy is possible together with the application of a magnetic field, there is an effect that allows for both magnetic field therapy using a skin invasive device and heat therapy through microneedles at the same time.

Therefore, the magnetic microneedles of the present disclosure can form magnetic nanoparticles inside the magnetic nanoparticle-containing tip of the microneedles formed of a shape memory polymer, thereby increasing the temperature of the magnetic nanoparticle-containing tip by an external magnetic field, thereby inducing the shape memory effect of the shape memory polymer microneedles, thereby allowing the shape of the microneedles to be continuously maintained. In addition, the amount of drug delivery can be controlled or maximized by controlling heat generation according to the magnetic field strength. In addition, when used together with an extracorporeal magnetic field therapy device, the magnetic nanoparticles can be heated by the extracorporeal magnetic field, thereby enabling heat treatment, and thus can be utilized in various medical fields such as moxibustion, drug delivery, heat therapy devices, heat-generating vascular stents, and bioelectrodes.

Below, the manufacturing method of the microneedle bioelectrode will be described in detail.

In another embodiment of the present disclosure, a method for manufacturing a microneedle bioelectrode may be provided, including: a step of manufacturing a microneedle structure in which a plurality of microneedles are arranged; a step of forming a microneedle mold by introducing the microneedle structure into a container containing a first polymer material; and a step of forming a microneedle array including a shape memory polymer; and a step of separating a hardened microneedle array from the microneedle negative mold to form a conductive layer including a conductive polymer on the surface of the microneedle array.

The microneedle structure manufacturing step (S100) and the microneedle mold forming step (S200) can be performed in the same manner as the microneedle array manufacturing method described above.

The microneedle array formation step (S300) will be described. The microneedle array formation step includes a shape memory polymer injection step (S310), a vacuum placement step (S320), and a microneedle array curing step (S350), and can be performed in the same manner as the microneedle array manufacturing method described above.

In one embodiment of the present disclosure, immediately after the microneedle array curing step (S350), the method may further include a step of activating the shape memory polymer surface of the separated microneedle array by treating the shape memory polymer surface with at least one plasma selected from the group consisting of O ₂ , Ar, and N ₂ .

The method of activating the surface of a shape memory polymer using the above plasma has the advantage of changing only the surface properties while maintaining the characteristics of the shape memory polymer even after plasma treatment. This plasma treatment generates unsaturated bonds or radicals on the surface of the shape memory polymer, and when coating the surface of the shape memory polymer with a conductive polymer, the conductive polymer and the shape memory polymer combine to produce an effect that improves adhesive strength.

The above conductive polymer coating step (S400) is a step of coating a conductive polymer on the surface of a shape memory polymer. This is a process of forming a conductive layer on the shape memory polymer that can detect a change in a biosignal or a change in a resistance value. In one embodiment of the present disclosure, the method of coating the conductive polymer on the surface of the shape memory polymer may be one or more methods selected from the group consisting of spray spin coating, spin coating, spray coating, inkjet printing, and dip coating. More specifically, the coating may be performed using spray spin coating.

After manufacturing the above microneedle electrode, it can be manufactured in the form of a microneedle bioelectrode patch that is easy to insert and attach to the skin by attaching it to a silicone liner, or it can be manufactured in the form of a sensor-attached silicone liner or exoskeleton robot band that can be used for a long time by combining it with the band part of an exoskeleton robot.

The microneedle bioelectrode manufactured according to the aforementioned microneedle bioelectrode manufacturing method also uses a 3D printing process to form the tip of the microneedle into an asymmetrical structure with an inclination of 30 to 60°, so that it can puncture the skin painlessly when attached to the body, and since it includes a shape memory polymer, it can avoid damaging skin tissue when inserted into the body.

Furthermore, by penetrating the skin with minimal invasion to measure biosignals, the present disclosure enables accurate detection of biosignals and bioresistance with less influence from noise, such as body movement. Therefore, the present disclosure provides a durable bioelectrode capable of reliably transmitting electrochemical signals within the body. Furthermore, the bioelectrode can be restored by heat or ultraviolet irradiation after use, enabling self-restoration and reuse.

Hereinafter, to aid in understanding of the present disclosure, a detailed description will be given through examples and the like. However, the embodiments according to the present disclosure are not limited to the embodiments described herein and may be modified in various other forms, and the scope of the present disclosure should not be construed as being limited to the following examples. The embodiments of the present disclosure are provided to more fully explain the present disclosure to those of ordinary skill in the art, and are provided only to sufficiently convey the spirit of the present disclosure to those skilled in the art.

[Example 1]: Fabrication of microneedle array.

After forming a microneedle structure using a 3D printer at an inclination angle of 45°, the microneedle structure was placed into a container containing PMDS to form a microneedle negative mold. At this time, the thickness of the base portion was set to 250 μm.

After injecting the shape memory polymer into the above microneedle engraving mold, it was placed in a vacuum chamber for approximately 30 minutes. Then, a doctor blade or scraper was set at 10 to 30 degrees to remove any excess shape memory polymer. The first curing was performed using ultraviolet light for 30 minutes. The second curing was performed in an oven under vacuum at 120 degrees Celsius for 24 hours, producing a microneedle array.

[Example 2]: Fabrication of a magnetic microneedle array.

In Example 1, a shape memory polymer containing magnetic nanoparticles, which is a mixture of a shape memory polymer and magnetic nanoparticles, was injected into the microneedle negative mold. The concentration of the magnetic nanoparticles was 5 mg/mL, but this can vary depending on various factors such as the intended use of the microneedle or the target temperature. A magnet can be placed at the bottom of the negative mold into which the shape memory polymer containing magnetic nanoparticles was injected to selectively increase the concentration of magnetic nanoparticles at the microneedle tip. Afterwards, as in Example 1, the mold was placed in a vacuum chamber for 30 minutes, and then a doctor blade or scraper set to 10 to 30 degrees was used to clean up any excess shape memory polymer. The first curing was performed using ultraviolet light for 30 minutes. The second curing was performed in an oven at 120 degrees Celsius in a vacuum for 24 hours, thereby manufacturing a microneedle array containing magnetic nanoparticles.

[Example 3]: Fabrication of a microneedle bioelectrode

After activating the surface of the shape memory polymer using _O2 plasma on the surface of the microneedle array manufactured in Example 1, the manufactured shape memory polymer microneedles were spun at 50 rpm and 4% PEDOT:PSS:PEG200 was spray-coated on the surface of the shape memory polymer to form a conductive polymer conductive layer, and then dried at 120°C for 30 minutes. Afterwards, the microneedle was immersed in methanol (or an organic solvent such as IPA or ethanol) and dried at 120°C for 30 minutes. The immersion time in the organic solvent can be adjusted as needed.

The shape of the fabricated microneedle bioelectrode is as shown in Fig. 5, and it can be inserted into the silicone liner of an amputee patient, and the amputee patient can accurately record electromyography signals for a long period of time without much discomfort.

[Comparative Example 1]: Surface electromyography (sEMG) electrode

A performance comparison experiment was conducted using a surface electromyography electrode that measures electromyography by attaching a surface electrode to the skin.

[Comparative Example 2]: Polyimide (PI) microneedle electrode.

Instead of shape memory polymers, microneedles were manufactured using polyimide (PI), and a performance comparison experiment was conducted with examples.

Experimental Example 1: Performance testing of a magnetic microneedle array.

Figure 8 illustrates the invention characteristics results of magnetic nanoparticles included in the magnetic microneedle array of Example 2.

Referring to Fig. 8, the heating characteristics of the magnetic nanoparticles manufactured in Example 2 when an oleic coating treatment is applied in ethanol and a specific magnetic field harmless to the human body is observed can be seen. Accordingly, it was confirmed that the magnetic nanoparticles exhibit heating characteristics of approximately 5℃ or higher in a specific magnetic field harmless to the human body, and the heating characteristics can be controlled by the amount of magnetic nanoparticles and the frequency and strength applied to the external magnetic field.

Figure 9 is a graph showing the results of the heat generation characteristics of the magnetic microneedle array of the present invention. Referring to Figure 9, the difference in temperature change between a magnetic microneedle array with magnetic nanoparticles concentrated at the tip through magnet arrangement and one without is evident. This indicates that heat is indeed concentrated and generated at the tip of the magnetic microneedles.

Figure 10 is a thermal imaging camera image showing the shape memory capability utilizing the heating characteristics of the magnetic microneedles of the present invention. Figure 10(a) shows the magnetic microneedles before applying a magnetic field, in a folded state. Figure 10(b) is a thermal imaging camera image of the magnetic microneedles after applying a magnetic field, confirming that heating has successfully occurred, and the shape recovery capability of the magnetic microneedles folded in half has been demonstrated, allowing them to unfold.

Experimental Example 2: Long-term use test of microneedle bioelectrodes.

Figure 20 illustrates a photograph of a microneedle bioelectrode attached to a patient with a lower extremity amputation. As shown in Figure 20, the microneedle bioelectrode manufactured according to the above example was attached to a patient with a lower extremity amputation and a patient with a femoral amputation, and tested to see if it could be used for an extended period of time without damage.

It was confirmed that the performance could be stably measured without change in electromyography signals even after continuous use for more than 8 hours in patients with lower leg amputations and more than 6 hours in patients with femoral amputations. It was also confirmed that no foreign body sensation or pain was felt inside the socket, so no discomfort was felt even after long-term use.

In addition, the durability of the microneedle bioelectrodes of Example 3 and Comparative Example 2 was tested.

Referring to Fig. 25, it was confirmed that the microneedle electrode of Comparative Example 2 underwent primary and secondary deformations when a force of approximately 8 N and 10 N was applied, and a fracture phenomenon occurred when a force of approximately 20 N was applied. In this case, there is a possibility that the microneedle may break within the skin tissue as a side effect when a small force is applied after insertion into the skin.

Fig. 16 shows the degree of deformation by applying force after using Example 3 of the present disclosure 1, 5, 10, 20, 30, 40, and 50 times. Referring to Fig. 16, it was confirmed that no breakage occurred even when a force of about 70 N was applied to the microneedle bioelectrode of the present disclosure after using it 50 times. In addition, referring to Fig. 25, it was confirmed that the microneedle bioelectrode of Example 3 did not break even when a force of about 80 N or more was applied, unlike Comparative Example 2. This confirms that the microneedle bioelectrode of the present disclosure has superior durability compared to Comparative Example 2.

Experimental Example 3: Performance comparison of surface electrodes and microneedle bioelectrodes.

A performance test was conducted on amputation patients using the microneedle bioelectrode produced in Comparative Example 1, which is a surface electrode that does not invade the skin, and Example 3 of the present disclosure.

Figure 21 shows the signal-to-noise ratio (SNR) measured in a treadmill exercise situation.

Referring to Fig. 21, in the comparative example in the treadmill exercise situation, the decrease in SNR was confirmed to increase over time, while in the embodiment using the microneedle bioelectrode, the decrease in SNR was confirmed to be lower than in the comparative example.

Next, frequency analysis was performed on the electromyography signals obtained using Example 3 and the comparative example. Referring to Fig. 12, it was confirmed that the surface electrode contained a large amount of 0-20 Hz signals corresponding to motion artifacts, i.e., motion noise caused by body movement, whereas the microneedle bioelectrode did not. This shows that the microneedle bioelectrode is hardly affected by motion artifacts and can therefore measure purer biosignals.

Furthermore, in a kicking situation, the electromyography signals obtained from surface electrodes and microneedle electrodes were compared. Referring to Figure 23, the microneedle electrode clearly distinguishes the electromyography signals when the foot is kicked and when the foot is folded, whereas the surface electrode does not clearly distinguish the signals and contains a significant amount of baseline noise. This confirms that the microneedle bioelectrode of the present disclosure is capable of measuring more accurate signals according to movement.

When measuring biosignals, weak signals due to skin thickness and various noises due to movement make accurate measurement and diagnosis difficult. However, looking at the above results, it was confirmed that the microneedle bioelectrode of the present disclosure is less affected by noise or noise due to movement or friction in measuring biosignals than the existing surface electrode. This is presumed to be because it is less affected by body movements such as the influence of skin thickness or noise due to movement by invasively penetrating the skin to measure biosignals and using a bioelectrode that includes a stretchable conductive polymer rather than a conventional metal thin film.

Therefore, the microneedle bioelectrode of the present disclosure can reduce the influence of various noises and measure purer biosignals more accurately and stably.

Experimental Example 4: Resilience test of microneedle bioelectrodes.

After using the microneedle bioelectrode, it was confirmed whether the performance of the electrode was restored to its initial state after the microneedle was restored to its original shape.

Figure 18 illustrates a microneedle bioelectrode that has been used 50 times, resulting in a slightly bent shape. After heating and restoring the microneedle bioelectrode after 50 uses, it was confirmed that it had recovered to the same shape as its initial state.

Referring to Figure 24, it can be confirmed that after 50 uses of the microneedle bioelectrode, the surface resistance is measured to be approximately 330Ω, which is higher than the initial state. However, after undergoing a recovery process at a temperature of 40℃, the electrode recovered to approximately 130Ω, which is the same surface resistance as the initial state.

In addition, referring to (b) of Fig. 24, it was confirmed that the surface resistance after cutting the microneedle bioelectrode with a razor blade was measured to be as high as approximately 1600Ω or more, but it was able to be restored to the same state as the initial state after recovery by heat.

On the other hand, referring to Figure 25, it was confirmed that in Comparative Example 2, the microneedles were broken when a force of 20 N was applied, and when force is applied to the microneedles as in Comparative Example 2, they are eventually broken and cannot be used again. In addition, if the electrode is bent or defective, the surface resistance becomes excessively large, making it impossible to measure biosignals, and the performance cannot be restored after a defect, making reuse impossible.

Accordingly, the microneedle bioelectrode of the present disclosure has good durability, and even if a defect occurs, it can be restored to an electrode with the same performance as the initial state by heat or infrared irradiation due to the recovery characteristics of the shape memory polymer and the conductive polymer, thereby providing a reusable bioelectrode.

While the embodiments of the present invention have been described above with reference to the attached drawings, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without altering the technical concept or essential features thereof. Therefore, the embodiments described above should be understood to be illustrative in all respects and not restrictive.

Claims (22)

Base section; and A plurality of microneedles formed to extend outward from one side of the base portion so that they can be inserted into the skin and whose shape is changed by external stimulation; A microneedle array, wherein the above microneedles include a shape memory polymer. In the first paragraph, The above shape memory polymer is a microneedle array that is a biocompatible shape memory polymer and is restored according to temperature or infrared irradiation. In the first paragraph, A microneedle array, wherein the shape memory polymer comprises at least one selected from the group consisting of 1,3,5-Triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO), Trimethylolpropane tris(3-mercaptopropionate) (TMTMP), Tricyclodecane dimethanol diacrylate (TCMDA), 2,2-dimethoxy-2-phenylacetophenone (DMPA), poly(methyl methacrylate), polyurethane, cross-linked polycaprolactone, polysilsesquioxane grafted with polyethylene glycol, and copolymers thereof. In the first paragraph, A microneedle array, wherein the tips of the microneedles have an asymmetric structure with an inclination of 30 to 60°. In the first paragraph, The tip of the above microneedle includes a tip portion containing magnetic nanoparticles, The above magnetic nanoparticles are nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O ₄ or nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O _4. A microneedle array, which is an alloy particle comprising iron oxide and at least one selected from the group consisting of magnesium (Mg), barium (Ba), manganese (mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr). In paragraph 5, A microneedle array in which the tip is heated by an alternating magnetic field applied from the outside of the base, and the physical properties of the microneedles are softened or the shape is deformed by the heating of the tip. A microneedle bioelectrode comprising a conductive layer comprising a conductive polymer on the entire surface of the microneedle array according to claims 1 to 6. In paragraph 7, A microneedle bioelectrode, wherein the conductive layer is at least one selected from the group consisting of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS), methanol-treated poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate): polyethylene glycol (methanol doped PEDOT:PSS:PEG200), MXene, and polypyrrole (PPy). In paragraph 7, The above microneedle bioelectrode is a microneedle bioelectrode for measuring a biosignal including any one of the group consisting of electrocardiogram, electromyogram, electroencephalogram, and nerve conduction. (S100) A step for producing a microneedle structure in which a structure in which microneedles are arranged in multiple rows is produced; (S200) A step of forming a microneedle mold by introducing the microneedle structure into a container containing the first polymer material; and (S300) A step of forming a microneedle array by injecting a shape memory polymer into a microneedle mold; A method for manufacturing a microneedle array comprising: In Article 10, The above microneedle structure is composed of a substrate portion and a plurality of microneedles protruding from the base portion, In the step (S100) of manufacturing the above microneedle structure, the above microneedle structure is manufactured using 3D printing, A method for manufacturing a microneedle array, wherein the above base portion is positioned at a certain angle of inclination with respect to the stage of a 3D printer. In Article 11, A method for manufacturing a microneedle array, wherein the base portion of the above microneedle structure is arranged at an angle of inclination of 30 to 60° relative to the stage of a 3D printer. In Article 10, In the above step (S300), magnetic nanoparticles are further injected into the negative mold, The above step (S300) is a vacuum placement step in which a mold into which a mixture of shape memory polymers and magnetic nanoparticles is injected is placed in a vacuum; A magnet placement step of placing a magnet on the outside of a microneedle mold placed in a vacuum in the above vacuum placement step; and A self-assembly step in which shape memory polymers and magnetic nanoparticles injected into the microneedle mold in which magnets are placed in the above magnet placement step are separated and self-assembled; A method for manufacturing a microneedle array, comprising: In Article 13, The above magnetic nanoparticles are nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O ₄ or nanoparticles of iron oxide containing Fe ₂ O ₃ or Fe ₃ O _4. A method for manufacturing a microneedle array, wherein the microneedle array is an alloy particle comprising at least one selected from the group consisting of iron oxide and magnesium (Mg), barium (Ba), manganese (Mn), cobalt (Co), nickel (Ni), zinc (Zn), gadolinium (Gd), and strontium (Sr). In Article 13, A method for manufacturing a microneedle array, wherein the size of the magnetic nanoparticles is 5 nm to 500 ㎛. Regarding a microneedle array manufactured according to Articles 10 to 15, A microneedle array, wherein the microneedle tips of the above microneedle array have an asymmetric structure with an inclination of 30 to 60°. In a skin invasive device that stimulates the skin by invading the skin using magnetic microneedles, A magnetic microneedle array comprising a plurality of microneedles that penetrate the skin; A depth control unit that fixes the plurality of microneedle arrays to control the depth at which they penetrate the skin; A substrate portion having a plurality of holes formed therein so that the plurality of microneedles can pass through and invade the skin; A magnetic field generating unit provided on the outside of the above substrate to generate a magnetic field; and A tip portion containing magnetic nanoparticles that generate heat by the magnetic field generating portion; A skin invasive device comprising: A step of manufacturing a microneedle array according to any one of claims 10 to 12; and (S400) A step of separating a microneedle array from the microneedle mold and forming a conductive layer including a conductive polymer on the surface of the microneedle array; A method for manufacturing a microneedle bioelectrode comprising: In Article 18, A method for manufacturing a microneedle bioelectrode, wherein the above microneedle array forming step (S300) includes a shape memory polymer injection step (S310) into a microneedle mold; a vacuum placement step (S320); and a microneedle array curing step (S350). In Article 18, A method for manufacturing a microneedle bioelectrode, further comprising a step of activating the shape memory polymer surface by treating the shape memory polymer surface with at least one plasma selected from the group consisting of O ₂ , Ar and N ₂ immediately after separating the microneedle array in the above step (S400). In Article 18, A method for manufacturing a microneedle bioelectrode, wherein the conductive polymer is at least one selected from the group consisting of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS), methanol-treated poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate): polyethylene glycol (methanol doped PEDOT:PSS:PEG200), MXene, and polypyrrole (PPy). A microneedle bioelectrode manufactured according to any one of claims 18 to 20.