Diagnosis-Treatment Integrated AI Closed-Loop Ear Patch and Neuromodulation Method Using the Same

Abstract

The present invention comprises a patch body fabricated by 4D printing that includes a shape memory polymer (SMP) whose shape changes in response to body temperature; a plurality of titanium microneedles provided on the patch body, each having a femtosecond laser-induced periodic surface structure (LIPSS) formed on its surface; an energy harvesting module comprising at least one of a triboelectric nanogenerator (TENG) or a piezoelectric nanogenerator (PENG) that generates power from a user's movement; an organic electrochemical transistor (OECT)-based biosensor that detects cortisol concentration from a user's biosignal; and the intensity, frequency, or output of a transcutaneous auricular vagus nerve stimulation (taVNS) signal applied through the microneedles based on the received data, which receives power from the energy harvesting module and receives cortisol concentration data from the biosensor. The present invention relates to a diagnosis-treatment linked AI closed-loop ear patch characterized by including an Edge AI control unit that controls at least one of the patterns in real time, and a drug delivery enhancement unit that controls the transdermal delivery and penetration depth of a drug using acoustic metamaterials or focused ultrasound.

Description

Technology Field

[0001] The present invention relates to neuromodulation technology including the auricular branch of the vagus nerve (ABVN) around the ear, and more specifically, to an artificial intelligence (AI)-based closed-loop ear patch that diagnoses a user's biosignal in real time and actively controls stimulation parameters, and a neuromodulation method using the same. Background Technology

[0002] Recently, as mental health issues such as stress, anxiety, and depression, as well as chronic pain and autonomic nervous system disorders, have emerged as major health problems in modern society, there is an increasing demand for non-invasive treatments with few side effects. Among these, Vagus Nerve Stimulation (VNS) is known to be effective for various conditions such as epilepsy and depression, and in particular, transcutaneous auricular VNS (taVNS), which stimulates the vagus nerve branches around the ear, is gaining popularity as a non-invasive method that does not require surgical intervention.

[0003] Existing related technologies included passive acupressure patches that apply continuous pressure by attaching to specific acupoints or nerve points, or simple electrical stimulation devices that apply constant electrical stimulation according to a set pattern. However, these technologies have the following limitations.

[0004] First, it is a static stimulation method that fails to reflect real-time changes in the user's physiological state. While the optimal stimulation intensity, frequency, and pattern may vary depending on an individual's condition or the time of day, existing devices operate only with preset values, resulting in limited therapeutic effects or difficulty in ensuring consistency.

[0005] Second, there is the issue of inefficient stimulation delivery caused by incomplete adhesion to the skin and movement. If the patch lifts off the skin surface or shifts in position due to user movement, the intensity and location of the stimulation change, making it difficult to achieve the intended neuromodulatory effect. This problem is particularly pronounced in highly curved areas such as the ears.

[0006] Third, there is the reduced stimulation efficiency and battery dependency caused by the high impedance of the skin. Since the skin has high electrical resistance, high energy is required to deliver effective stimulation; this increases battery consumption and has become a limitation on the miniaturization and long-term use of the device.

[0007] Therefore, there is an urgent need to develop a new type of intelligent neuromodulation system that actively regulates stimulation by monitoring the user's biosignals in real time, maximizes stimulation efficiency by adhering perfectly to the skin, and operates by self-generating power without an external power supply. Meanwhile, prior art literature related to the present invention includes U.S. Patent Application Publication US2017 / 0258995, U.S. Patent Publication US11660265, the paper by Ok, Jehyung et al. (Advanced Materials), U.S. Patent Application Publication US2006 / 0122675, and the paper by Mugo, Samuel M. et al. (Electrochemical Science Advances). The problem to be solved

[0008] The present invention was devised to solve the problems of the prior art described above, and its first objective is to implement an AI-based closed-loop system that diagnoses a user's biosignals in real time and actively controls therapeutic stimuli.

[0009] The second objective of the present invention is to provide an ear patch that uses 4D printing technology to perfectly fit the curves of the user's body, ensuring consistency and efficiency in stimulation delivery.

[0010] The third objective of the present invention is to increase stimulation efficiency by drastically lowering skin impedance through microneedles using femtosecond laser processing technology.

[0011] The fourth objective of the present invention is to provide an ear patch capable of self-driving without an external power source or battery through energy harvesting technology.

[0012] The fifth objective of the present invention is to provide a source technology that maximizes the therapeutic efficacy of neuromodulation by creating a synergistic effect through the organic combination of the above components that cannot be predicted by a simple combination of existing technologies. means of solving the problem

[0013] A diagnosis-treatment linked AI closed-loop ear patch according to an embodiment of the present invention for solving the above technical problem comprises: a patch body fabricated by 4D printing that includes a shape memory polymer (SMP) whose shape changes in response to body temperature; a plurality of titanium microneedles provided on the patch body, having Femtosecond Laser-Induced Periodic Surface Structures (LIPSS) formed on their surfaces; an energy harvesting module comprising at least one of a triboelectric nanogenerator (TENG) or a piezoelectric nanogenerator (PENG) that produces power from a user's movement; and an organic electrochemical transistor (OECT)-based biosensor that detects cortisol concentration from a user's biosignal. The device is characterized by including an Edge AI control unit that receives power from the energy harvesting module, receives cortisol concentration data from the biosensor, and controls in real time at least one of the intensity, frequency, or output pattern of a transcutaneous vagus nerve stimulation (taVNS) signal applied through the microneedle based on the received data, and a drug delivery enhancement unit that controls the transcutaneous delivery and penetration depth of a drug using an acoustic metamaterial or focused ultrasound.

[0014] Additionally, the present invention may further include a drug delivery enhancement unit that controls the transdermal delivery and penetration depth of a drug using an acoustic metamaterial or focused ultrasound; or a soluble microneedle in which the microneedle is made of a biodegradable polymer and dissolves within the skin to release the drug contained therein.

[0015] A neuromodulation method according to another embodiment of the present invention for solving the above problem comprises: (a) attaching the above-described AI closed-loop smart patch to the skin around the user's ear; (b) measuring the user's cortisol concentration in real time through a biosensor of the patch; (c) determining an optimal taVNS stimulation parameter based on the measured cortisol concentration by an edge AI controller of the patch; and (d) applying a taVNS stimulation signal through the microneedle according to the determined stimulation parameter by the edge AI controller. Effects of the invention

[0016] The diagnosis-treatment linked AI closed-loop smart patch according to the present invention has the following effects.

[0017] First, personalized active treatment is possible. Through a closed-loop system that monitors cortisol levels, a stress hormone, in real time using an OECT sensor and uses edge AI to analyze this data to immediately adjust the intensity and frequency of taVNS stimulation, it is possible to provide personalized neuromodulation treatment most optimized for the user's current condition. This maximizes therapeutic effects compared to existing technologies that provided only static stimulation.

[0018] Second, it dramatically improves the efficiency and consistency of stimulation. The patch body, made of 4D-printed SMP material, perfectly self-deforms and adheres to the curvature of the user's ear due to body temperature, ensuring stable stimulation delivery without lifting. In addition, titanium microneedles with femtosecond LIPSS nanostructures significantly lower the electrical impedance of the skin, enabling the delivery of effective nerve stimulation with less energy.

[0019] Third, it maximizes user convenience. Through TENG / PENG energy harvesting technology, it generates the power required for operation solely from the user's daily movements, enabling semi-permanent use without the need for separate battery replacement or charging.

[0020] Fourth, it creates unpredictable synergistic effects. The present invention is not merely a combination of known technologies, but rather, each component—'thermodynamic 3D self-deformation adhesion (4D SMP)', 'nanostructure-based impedance control (LIPSS microneedle)', 'battery-free self-generation (TENG / PENG)', and 'real-time diagnosis-treatment integration (OECT sensor + AI closed loop)'—interacts organically to produce a significant increase in effect that cannot be predicted by the sum of existing technologies; that is, it exhibits heterogeneity in composition and effect. This is a unique technical feature of the present invention that cannot be achieved by simple substitution of components or numerical limitations. Brief explanation of the drawing

[0021] FIG. 1 is a schematic diagram showing the overall configuration of a diagnosis-treatment linked AI closed-loop ear patch according to one embodiment of the present invention. FIG. 2 is a schematic diagram showing the process in which the patch body of the present invention is attached to the user's ear and then deformed by body temperature to adhere closely. Figure 3 is an example of an enlarged electron microscope image of a femtosecond LIPSS structure formed on the surface of a titanium microneedle applied to the present invention. Figure 4 is a flowchart illustrating the diagnosis-treatment linked closed-loop control process of the present invention. FIG. 5 is a schematic diagram illustrating the principle of drug delivery enhancement using an acoustic metamaterial, which is an optional component of the present invention. Specific details for implementing the invention

[0022] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings. However, the present invention is not limited to the embodiments disclosed below but can be implemented in various different forms, and the embodiments provided are merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention.

[0023] 1. Overall configuration of the ear patch (see Fig. 1)

[0024] The AI ​​closed-loop ear patch (100) according to the present invention largely comprises a patch body (110), a microneedle array (120), an energy harvesting module (130), a biosensor (140), and an edge AI control unit (150). These can be integrally configured on a flexible substrate.

[0025] a. Patch body (110)

[0026] The patch body (110) serves to maintain the overall shape of the ear patch and support each component. In the present invention, the patch body (110) is manufactured using 4D printing technology and uses shape memory polymer (SMP) as the main material. SMP has the characteristic of easily deforming when heated above a specific temperature (transition temperature, Tg), maintaining its shape upon cooling, and returning to its originally programmed shape when heated above the transition temperature again.

[0027] In the present invention, an SMP is used with the human body temperature (approx. 36.5°C) set as the transition temperature. When the ear patch is attached to the skin, the patch body (110) softens due to the user's body temperature and deforms along the complex and irregular curves of the ear to adhere perfectly (see FIG. 2). This creates contact optimized for the individual user's ear shape, much like a custom earphone, preventing the ear patch from lifting or shifting position and ensuring that the micro-needles (120) make contact with the intended nerve stimulation point with accurate and consistent pressure.

[0028] Existing acupressure patches use flat medical tape (e.g., 3M tape) to attach to the highly curved and three-dimensional surface of the ear, so the adhesive strength rapidly deteriorates due to skin secretions or movement, and there is a fatal limitation in that the three needle tips cannot stimulate the reflex zones with uniform pressure.

[0029] In particular, the cavity and cymbal conchae, which are major reflex zones of the ear, have a three-dimensional concave structure, making it impossible to adhere them to flat substrates. As the first innovative component to fundamentally solve this problem, '4D printing-based thermo-responsive shape memory polymer (trSMP)' substrate technology was introduced.

[0030] 4D printing is an advanced additive manufacturing technology that combines a four-dimensional element called 'Time' with structures produced by traditional 3D printing, allowing them to self-morphe into a pre-programmed three-dimensional shape when exposed to specific external stimuli such as heat, light, moisture, and magnetic fields.

[0031] The patch substrate applied in the present invention may be provided to use a nanocomposite based on a mixture of polyurethane (PU), polycaprolactone (PCL), and polyacrylic acid (PAAc), which is precisely designed at the molecular level to have a glass transition temperature or melting temperature near 36 to 37°C, which is the normal human body temperature range.

[0032] The operating principle of this shape memory polymer is based entirely on the entropic restoring forces of the polymer chains. When the patch is inside the packaging at room temperature (about 20–25°C), the crystallites or hydrogen bonding networks inside the polymer can be configured to temporarily fix the shape in a deformed form (a flat coin shape that is easy to attach).

[0033] When a user lightly places the patch on the reflex zone of the ear, the temperature of the patch gradually rises due to body heat transferred through contact with the skin. When this critical temperature is reached, the crystallization of the polymer chains is released and the dynamic fluidity of the chains increases, releasing the elastic energy accumulated internally during the printing process. As a result, the patch can be equipped to self-deform into a three-dimensional permanent shape programmed in advance by a 4D printing algorithm without external physical manipulation, that is, into an anchor shape that accurately wraps around and deeply penetrates the concha curve and antihelix of the ear.

[0034] The shape recovery rate (Rr) and shape fixation rate (Rf), which evaluate the performance of this shape recovery process, are defined by the following thermodynamic formulas, and the composite material introduced in this invention achieves an overwhelming recovery efficiency of over 96%.

[0035]

[0036]

[0037] In this formula The maximum mechanical strain applied to the material, Permanent strain remaining after the completion of the cycle, ε represents the temporary strain after the removal of the stress load, and N represents the number of repeated thermal-mechanical cycles.

[0038] The essence of the effect created by this component lies in the fact that, regardless of individual differences in the anatomical structure of the user's ear, it generates a perfect conformal fit in response to body temperature, thereby fundamentally preventing the stimulating electrode from peeling off the skin and continuously providing uniform subcutaneous pressure. This completely replaces the passive attachment method that relied on conventional medical 3M tape with molecular-level smart material technology.

[0039] b. Microneedle array (120)

[0040] A microneedle array (120) composed of multiple microneedles is placed on the skin contact surface of the patch body (110). The microneedles penetrate the stratum corneum, the outermost layer of the skin, with minimal pain to access nerve endings or drug delivery pathways.

[0041] In the present invention, the microneedles are made of titanium, which has excellent biocompatibility, and a key feature is that a femtosecond laser-induced periodic surface structure (LIPSS) is formed on its surface (see Fig. 3). LIPSS is a phenomenon in which a periodic pattern of tens to hundreds of nanometers in size, smaller than the wavelength of the laser, is self-assembled when a femtosecond ultrashort pulse laser is irradiated onto the surface of a material.

[0042] The nanoscale wrinkle structure formed in this way maximizes the surface area of ​​the microneedles and promotes electrochemical reactions at the interface with skin tissue, thereby drastically reducing the electrical impedance of the skin. This is based on a principle similar to how coarse sandpaper has greater friction than a smooth surface. When skin impedance is lowered, much lower voltage and current can be used to produce the same nerve stimulation effect, thereby increasing the efficiency of stimulation and reducing energy consumption.

[0043] Existing patent literature simply explains that titanium is mechanically polished to form three conical needle-like peaks, and microcurrents are generated on the skin through a natural oxide film formed upon exposure to air.

[0044] However, from a neurophysiological perspective, the human stratum corneum has very high electrical resistance (on the level of several hundred kΩ), making it impossible to generate the clinically effective potential difference and penetration depth required for actual vagus nerve stimulation (taVNS) using only mechanically polished simple metal protrusions and natural oxide films.

[0045] As a second key component to overcome this, the present invention may be equipped to fully apply ultra-precision LIPSS (Laser-Induced Periodic Surface Structures) nanostructures generated by irradiating a femtosecond laser onto the surface of the stimulating microneedle.

[0046] LIPSS refers to a nanoscale periodic ripple structure formed by the minute interference phenomenon between the incident electromagnetic waves and surface scattered waves (or surface plasmon polaritons, SPP) flowing along the metal surface when an ultrashort laser pulse of picosecond or femtosecond scale is irradiated onto a metal surface.

[0047] When a femtosecond laser with a wavelength of 1026 nm or 513 nm is irradiated onto a titanium alloy surface with precise control of the fluence and number of pulses, a complex hierarchical micro-nano structure is formed in which LSFL (Low Spatial Frequency LIPSS) with a low-frequency spatial period in a direction perpendicular or parallel to the laser polarization direction and HSFL (High Spatial Frequency LIPSS) with a high-frequency period are fused.

[0048] The effects of the present invention resulting from the introduction of such LIPSS-treated titanium electrodes into the acupressure patch invention are as follows.

[0049] First, there is the maximization of the effective surface area and the exponential reduction of contact impedance. Although the nano-ripple structure appears smooth macroscopically, it is composed of numerous irregularities microscopically, which strongly induces mechanical interlocking upon contact with the stratum corneum of the skin.

[0050] This drastically reduces the electrode-skin contact impedance to a fraction of the conventional level, even in dry, sweat-free skin environments, enabling effective charge transfer at very low voltages.

[0051] Second, there is the artificial control of oxide film characteristics and the significant amplification of microcurrents. The ultrafast thermodynamic changes occurring during the LIPSS formation process go beyond simple amorphous natural oxide films and induce the formation of thin, uniform, and highly crystalline rutile phases and titanium nitride.

[0052] This composite oxide-nitride film, generated in an environment with controlled nitrogen partial pressure, exhibits significantly superior conductivity and charge transfer capabilities compared to conventional natural oxide films. Furthermore, upon contact with skin electrolytes, it triggers a powerful electrochemical ionization reaction that dramatically amplifies the efficiency of self-microcurrent generation.

[0053] Third, there is an increase in biocompatibility and cell affinity. The nano-roughness induced by LIPSS promotes the attachment and diffusion of keratinocytes while providing an excellent anti-biofouling effect that inhibits the formation of bacterial film, thereby fundamentally preventing skin troubles or inflammation even when the patch is attached for several days.

[0054] In the present invention, the conventional rough and coarse three-needle structure is discarded, and an advanced bio-interface electrode is designed to maximize permeability to the skin without pain by 3D patterning the entire surface of hundreds of thin titanium micro-needle arrays with LIPSS.

[0055] c. Energy harvesting module (130)

[0056] The energy harvesting module (130) is a self-generating device that produces driving energy on the ear patch itself without an external power supply. In the present invention, a triboelectric nanogenerator (TENG) or a piezoelectric nanogenerator (PENG) is used.

[0057] TENG generates electricity by utilizing static electricity generated when two different materials come into contact, separate, or rub against each other. Everyday movements, such as walking or talking while the ear patch is attached, induce minute pressure and friction, which TENG converts into electrical energy.

[0058] PENG utilizes the principle that voltage is generated by the polarization of electric charges within the material when pressure or vibration is applied, based on the piezoelectric effect.

[0059] This energy harvesting module (130) continuously produces and supplies sufficient power to drive the biosensor (140) and edge AI controller (150), thereby enabling a battery-less wearable device.

[0060] Since the existing invention relies solely on minute amounts of microcurrents resulting from the chemical ionic reactions of the titanium material itself in the absence of an external power source within the patch, the brain neurotransmission effect of the stimulation is extremely minimal and unsustainable.

[0061] In order to reliably obtain clinical physiological effects such as fatigue recovery, reduction of hyperarousal stress response, and stabilization of heart rate variability (HRV) by actively regulating the brain's neural network, transcutaneous auricular vagus nerve stimulation (taVNS), which directly stimulates the auricular branch of the vagus nerve (ABVN) that is widely distributed in the concha of the ear with electrical pulses, is essential.

[0062] However, incorporating a traditional lithium battery into the patch increases the device's volume and weight, severely compromising the user's aesthetic and physical comfort. To technically overcome this, the core component of the present invention is the integration of a hybrid biomechanical energy harvesting module in which a triboelectric nanogenerator (TENG) and a piezoelectric nanogenerator (PENG) are combined on the same flexible substrate.

[0063] This hybrid nanogenerator captures minute movements of the muscles and ligaments around the ear, specifically the periodic movements of the temporomandibular joint that inevitably occur when a user speaks or chews food, and even the pulsating energy of the temporal artery around the ear, and converts it back into electrical energy.

[0064] The TENG module consists of two flexible polymer films, such as polytetrafluoroethylene (PTFE) and nylon, which have distinctly different electron affinities in the triboelectric series. Depending on the minute movements of the mandible, these two films behave in a repetitive contact-separation mode behind the ear or inside the auricle, generating strong static electricity.

[0065] Open circuit voltage generated in TENG ( ) is the dynamic distance between two contact surfaces ( ) and surface charge density( ), and vacuum permittivity ( It follows the following electromagnetic governing equations by ).

[0066] The PENG module combined in parallel with this is composed of lead zirconate titanate (PZT) nanoparticles or a layer of PVDF-TrFE (Polyvinylidene fluoride-trifluoroethylene), a polymer piezoelectric material, and generates a continuous alternating voltage by the piezoelectric effect when the patch itself is deformed by the shape memory polymer or subjected to contraction / relaxation stress of the skin.

[0067] The harvested kinetic energy in microwatt (μW) units is rectified into a DC pulse via a micropower management integrated circuit (Power Management IC) and then transmitted to the vagus nerve as a short square wave electrical stimulus through the previously described LIPSS-treated microneedle electrode.

[0068] According to recent immunopharmacology and neurology studies, the efficacy of the PENG-based self-driven taVNS system has been clearly demonstrated by attenuating cardio-brain neuroremodeling in a myocardial infarction (MI) model and alleviating neuroinflammatory responses via macrophages and microglia within the central amygdala (CeA), thereby significantly improving emotional disorders such as depression and stress.

[0069] This battery-free, self-powered taVNS fusion offers significant effects that are on a completely different level from existing manual acupressure patches.

[0070] D. Biosensor (140) and edge AI control unit (150) (closed-loop system)

[0071] The diagnosis-treatment linked closed-loop system, which is the core of the present invention, is implemented through the interaction of a biosensor (140) and an edge AI control unit (150) (see FIG. 4).

[0072] The biosensor (140) detects the cortisol hormone, known as an objective indicator of stress, in real time. To this end, it uses an organic electrochemical transistor (OECT)-based sensor with high sensitivity and selectivity. It detects changes in the concentration of trace amounts of cortisol contained in the interstitial fluid of the skin or sweat, which are accessible through microneedles, by converting them into electrical signals.

[0073] The edge AI control unit (150) is equipped with an artificial intelligence algorithm on a low-power microcontroller (MCU) and continuously receives cortisol concentration data from a biosensor (140) (S401). When the AI ​​model within the control unit determines that the received cortisol level is in a stress state, such as exceeding a preset threshold or showing a rapid upward pattern (S402), it calculates and determines optimal taVNS stimulation parameters in real time to alleviate the stress (S403). The parameters determined include the intensity of stimulation (voltage / current), frequency (Hz), pulse width (μs), stimulation time, and interval. For example, adaptive control is performed by increasing the stimulation intensity of a specific frequency band (e.g., 25Hz) that activates the parasympathetic nervous system as the cortisol level increases, or by increasing the stimulation time.

[0074] According to the determined parameters, the edge AI control unit (150) generates the corresponding taVNS signal through the stimulation generation circuit and applies it to the user through the microneedle array (120) (S404). This completes a complete AI closed loop leading from 'diagnosis (cortisol detection) → analysis (AI judgment) → treatment (customized stimulation)'.

[0075] The present invention may be provided by the integration of an Organic Electrochemical Transistor (OECT) biosensor that directly and quantitatively analyzes the concentration of the major stress hormone cortisol in real time from fine sweat or superficial interstitial fluid (ISF) around the ear, and a micro-AI closed-loop system that processes this data at the edge.

[0076] Cortisol is a hormone secreted by the adrenal cortex and is the most important key biomarker that objectively indicates the level of acute physical and mental stress in humans.

[0077] However, cortisol secretion exhibits a strong circadian rhythm that fluctuates throughout the day, and conventional methods of blood sampling or saliva collection in hospitals only provide fragmentary figures at specific points in time, making continuous real-time monitoring impossible.

[0078] The OECT-based sensor incorporated in the present invention may be provided with a multilayer transistor structure in which a molecularly imprinted polymer (MIP) or a specific DNA aptamer is coated as an ultrathin film on a conductive polymer PEDOT:PSS (Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) channel to selectively capture only target molecules.

[0079] When finely sweated from the skin on the surface of the ear flows into the OECT sensor via capillary action through microfluidic channels inside the shape-memory polymer patch, cortisol molecules contained in the sweat stereospecifically bind to MIP or aptamer structures.

[0080] This coupling reaction instantly changes the distribution of charge carrier (ion) concentration and electrostatic potential inside the channel, and consequently drastically changes (reduces) the channel current flowing between the source and drain electrodes of the OECT.

[0081] Thanks to OECT's unique signal amplification function, this method has a much higher transconductance than conventional enzyme-based electrochemical sensors, enabling the immediate detection of minute waveforms of ultra-trace amounts of cortisol in picomolar (pM) or nanomolar (nM) ranges without delay.

[0082] The detected continuous cortisol data values ​​and multi-modal biosignals such as parallel acquired heart rate variability (HRV) and brain waves (Ear-EEG) are transmitted to an ultra-power edge computing AI microcontroller integrated within the patch. The AI ​​algorithm evaluates the time-series trajectory of the user's current stress level and anxiety state, and if signs of acute stress (an abnormal surge in cortisol graph) are detected, it immediately applies the energy harvested and stored from the previously described TENG / PENG generator to the LIPSS electrode to automatically initiate active vagus nerve stimulation (taVNS).

[0083] Parameters such as the frequency of stimulation, frequency (e.g., 10 Hz or 25 Hz), and pulse width are adaptively controlled in real time by AI until the cortisol level returns to the baseline, and the stimulation is immediately stopped to conserve energy when the cortisol level is fully stabilized.

[0084] This can constitute a biofeedback closed-loop system that continuously monitors and diagnoses the state of disease or stress, while simultaneously autonomously performing immediate neuromodulation therapy to alleviate it within a single wearable device without external intervention.

[0085] Table 1 below is a logic matrix showing how each sensing parameter is converted into a taVNS stimulation protocol within the AI ​​system to achieve closed-loop control.

[0086] Primary biomarker (input) Second-order correlation data (multimodal) AI-identified stress / disease status AI-driven active control output (taVNS and acoustic control) Cortisol levels surge by more than 10% Increase in lactic acid, rise in skin conductivity (EDA) Manifestation of acute anxiety / psychological stress Immediate application of high-frequency (25Hz) taVNS stimulation via LIPSS electrodes 83 Reduction in heart rate variability (HRV) Ear-EEG Theta / Alpha Wave Variation 24 Excessive activation of the sympathetic nervous system Low-frequency (10Hz) taVNS continuous stimulation and PENG energy harvesting enhancement Maintaining a sustained elevation of cortisol TENG voltage surge due to detection of Bruxism Accompanied by chronic stress and physical pain Acoustic Metamaterial Module Driving: Transdermal Administration of Pain Reliever via Ultrasonic Cavitation Induction 64

[0087] 2. Optional Examples

[0088] In addition to the essential components mentioned above, the present invention may include optional components to further extend therapeutic efficacy.

[0089] a. Drug delivery enhancement section (see Fig. 5)

[0090] The ear patch of the present invention may further include a drug delivery enhancement unit utilizing acoustic metamaterials or focused ultrasound. Acoustic metamaterials are structures that concentrate energy at a specific point by controlling the wavelength of sound or ultrasound. By applying minute mechanical vibrations to the surface of the skin to temporarily increase skin permeability, this helps to deliver drugs or active ingredients contained in the ear patch deep into the skin. This can be usefully employed when seeking to simultaneously achieve neuromodulatory effects and drug therapeutic effects.

[0091] The present invention may be configured to include an active ultrasonic stimulation and transmission patch structure integrated with an acoustic metamaterial for non-invasive control of deep tissue beyond simple surface electrical stimulation or surface pressure.

[0092] Acoustic metamaterials are sub-wavelength structures artificially designed to possess negative mass density or negative bulk modulus, which are not found in naturally occurring materials.

[0093] The inner layer of this intelligent acupressure patch may be equipped to include fine interdigital transducers (IDTs) and an acoustic impedance matching layer.

[0094] When a portion of the power produced by the previously described hybrid TENG / PENG generator is used to apply an electrical signal of a specific frequency to the IDT, surface acoustic waves (SAW) are generated intensively by the thin piezoelectric film layer.

[0095] This acoustic metamaterial array highly focuses generated multidirectional ultrasonic energy to induce 'acoustic cavitation' in the microfluidic regions within the skin surface and stratum corneum. The micro-jet currents produced by the collapse of microbubbles generated by cavitation temporarily disrupt the rigid lipid bilayer structure of the epidermal stratum corneum, which consequently has the effect of maximizing the macroscopic permeability of the skin tissue in a short period.

[0096] When Triptolide, a treatment for arthritis and local pain, or a trace amount of a drug for acute stress relief (e.g., epinephrine or lidocaine) is loaded into a hyaluronic acid and polyvinylpyrrolidone (PVP)-based soluble microneedle, and ultrasonic energy from an acoustic metamaterial is applied at specific times and intensities (multi burst), the penetration depth and release kinetics of the drug can be digitally and precisely programmed.

[0097] That is, it can be equipped with a mechanism in the form of a fused diagnosis-physical therapy-drug therapy that generates a maximized virtual 'physical acupressure effect' with no pain at all by applying physical impact and acoustic streaming deep into the dermis layer through acoustic radiation force, while simultaneously combining biochemical drug treatment if necessary.

[0098] B. Dissolvable microneedles

[0099] In another embodiment, the microneedle (120) itself can be made of a biodegradable polymer such as hyaluronic acid. In this case, a specific drug that helps stabilize nerves (e.g., a serotonin precursor) or a functional ingredient can be impregnated inside the microneedle. After attaching the ear patch, as the microneedle gradually dissolves due to moisture in the skin, the active ingredient inside is directly released, allowing for a synergistic effect that provides both electrical and chemical stimulation simultaneously. Explanation of the symbols

[0100] Patch body: 110 Microneedles: 120

Claims

Claim 1 A patch body fabricated by 4D printing comprising a shape memory polymer (SMP) that changes shape in response to body temperature; a plurality of titanium microneedles provided on the patch body, having Femtosecond Laser-Induced Periodic Surface Structures (LIPSS) formed on their surfaces; an energy harvesting module comprising at least one of a triboelectric nanogenerator (TENG) or a piezoelectric nanogenerator (PENG) that generates power from a user's movement; and an organic electrochemical transistor (OECT)-based biosensor that detects cortisol concentration from a user's biosignals. An ear patch characterized by comprising: an Edge AI control unit that receives power from the energy harvesting module and receives cortisol concentration data from the biosensor, and controls in real time at least one of the intensity, frequency, or output pattern of a transcutaneous auricular Vagus Nerve Stimulation (taVNS) signal applied through the microneedle based on the received data; and a drug delivery enhancement unit that controls the transdermal delivery and penetration depth of a drug using an acoustic metamaterial or focused ultrasound. Claim 2 The ear patch according to claim 1, wherein the patch body softens due to body temperature when attached to the user's skin and deforms according to the curved surface of the ear to provide a snug fit. Claim 3 An ear patch according to claim 1, characterized in that the LIPSS formed on the surface of the microneedle reduces electrical impedance at the contact interface with the skin, thereby increasing the taVNS stimulation efficiency. Claim 4 The ear patch according to claim 1, wherein the edge AI control unit is configured to apply taVNS stimulation in a frequency band that activates the parasympathetic nerve when the cortisol concentration detected by the biosensor exceeds a set threshold. Claim 5 delete Claim 6 An ear patch according to claim 1, wherein the microneedles are made of a biodegradable polymer and contain a drug inside, and release the drug as they dissolve in moisture within the skin.

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