WO2015141988A1

WO2015141988A1 - Multifunctional wearable electronic device and manufacturing method therefor

Info

Publication number: WO2015141988A1
Application number: PCT/KR2015/002446
Authority: WO
Inventors: 김대형; 현택환; 손동희; 이종하
Original assignee: 서울대학교 산학협력단; 기초과학연구원
Priority date: 2014-03-18
Filing date: 2015-03-13
Publication date: 2015-09-24
Also published as: KR101738612B1; KR20150108580A

Abstract

The present invention relates to a multifunctional wearable electronic device and a manufacturing method therefor. More specifically, the present invention relates to a wearable electronic device comprising: a biocompatible film capable of being adhered to skin; and stretchable and flexible electronic elements attached to the biocompatible film, and a manufacturing method therefor.

Description

Multifunctional wearable electronic device and manufacturing method thereof

The present invention relates to a multifunctional wearable electronic device and a manufacturing method thereof. More specifically, the present invention relates to a wearable electronic device comprising a biocompatible film adhereable to the skin, stretchable and flexible electronic devices attached to the biocompatible film, and a method of manufacturing the same.

Wearable electronic devices refer to electronic devices that can always be used in need because they can be worn on the human body. In recent years, wearable electronics are expected to play an important role in the future of human life. Among the wearable devices, in order to implement a high-performance electronic device that can be attached to the skin, which is thin and light, an extensible electronic device is manufactured using a very thin thin film and a tortuous electrode. In addition, these devices are placed in a neutral mechanical plane between the polymer layers to protect brittle devices.

Devices equipped with wearable sensors that can continuously measure important physiological parameters and combine data storage and drug delivery are expected to revolutionize personal healthcare. However, despite the fact that conventional monitoring devices only capture noteworthy physiological data, the form factor of existing devices prevents seamless integration into the skin, limiting wearability problems and signal to noise. A problem arises.

To date, qualitative physiological parameters used to monitor diseases such as Parkinson's disease have been tracked through coarse monitoring cycles through video surveillance and delivery. However, to understand the progression of Parkinson's disease and other neurological disorders for drug therapy, there is a need for quantitative evaluation and pattern analysis of physiological parameters from the recorded data. In addition, compliance with oral administration on a daily basis is at risk of side effects in the case of non-adherence and overdose. The efficacy of drug therapy thus relies heavily on strategic dosing, including controlled and sustained release transdermal delivery, and continuous monitoring of the patient's indications for daily regimen.

Electronic systems comprising inorganic and organic nanomaterials in flexible and stretchable structures, due to their increased convenience, are particularly powerful alternatives to bulky health monitoring devices, thereby improving compliance. do. These emerging electronic devices include sensors, light emitting diodes, and associated circuit elements that come in contact with internal organs (eg, heart, brain), skin, or through an artificial skin scaffold. However, a major limitation on such flexible and stretchable electronic devices for the wearable biomedical device is that no portable memory module has yet been implemented that can store recorded data in real time during continuous long-term monitoring. Another feature required for emerging wearable devices is the ability to perform advanced treatment in response to diagnostic patterns present in the collected data.

Resistive random access memory (RRAM), made from oxide nanomembrane (NM), is a type of high performance nonvolatile memory that is emerging today. Conventional RRAM devices constructed on rigid substrates are made of a hard and brittle material, which tends to be mechanically incompatible with soft tissue that is curved and dynamically deformed. Although organic non-volatile memory enables flexible data-storage fabrication, there are still limitations such as high power consumption, insufficient reliability and lack of fitness. Similarly, incorporation of drug delivery devices consisting of a robust microfluidic pump or a rigid electronic stimulator can cause serious problems in mechanical integration of the human body with wearable electronics.

Conventional wearable devices mostly form electronic devices on rigid substrates and are simply wearable / wearable. These devices can actually wear / wear, but have the disadvantage that they are uncomfortable in daily life due to their bulky weight and relatively heavy weight.

US Patent Application Publication No. 20130041235 discloses a wearable device in which thin and light electronic devices are implanted into the skin. However, according to the above technology, since the electronic devices are positioned on the sacrificial polymer layer, the wearable device is implanted into the skin through a method of placing the sacrificial polymer layer on the skin and then removing the sacrificial polymer layer. However, in this case, since the wearable device is continuously exposed to foreign substances on the skin and also may cause inflammation to the skin in the long term, there are many problems to be used for medical purposes.

The present invention implements this type of stretchable, thin and light wearable electronic device on a medical patch or band to enable a medical examination in daily life, and based on this, an integrated system for additional medical treatment in the form of drug delivery. It relates to the concept of and a method of manufacturing the same.

It is a primary object of the present invention to provide a multifunctional wearable electronic device comprising a biocompatible film attachable to the skin and a stretchable and flexible electronic device attached to the biocompatible film.

Another object of the present invention is to provide a method of manufacturing a multifunctional wearable electronic device, comprising attaching the stretchable and flexible electronic device to a biocompatible film that is adhereable to the skin.

Still another object of the present invention is to (i) coating and curing poly (methyl methacrylate) and the first polymer on a silicon substrate in turn; (ii) patterning the first polymer layer; (iii) fabricating an electronic device adjacent to the first patterned polymer layer; (iv) forming a second patterned polymer layer adjacent the electronic device; (v) removing the silicon substrate and the poly (methyl methacrylate) to obtain a device encapsulated with the first polymer and the second polymer; (vi) removing the poly (methyl methacrylate) layer from the device encapsulated with the first polymer and the second polymer and attaching to the elastic substrate; And (vii) attaching the device having the poly (methyl methacrylate) layer removed from the elastic substrate to a biocompatible film attachable to the skin, wherein the first patterned polymer layer and the second patterned It is to provide a method of manufacturing a wearable electronic device, wherein each of the first electrode and the second electrode of the electronic device adjacent to the polymer layer is patterned.

The basic object of the present invention described above can be achieved by providing a wearable electronic device comprising a biocompatible film attachable to the skin and stretchable and flexible electronic elements attached to the biocompatible film.

In the wearable electronic device of the present invention, the biocompatible film may be a polyurethane film coated with a hydrocolloid adhesive.

In addition, the surface of the biocompatible film (patch) is coated with a hydrocolloid adhesive, drug-filled mesoporous silica nanoparticles or biodegradable polymer nanoparticles may be included. While the drug filled in the mesoporous silica nanoparticles or biodegradable polymer nanoparticles is released, it can be absorbed by the human body through the skin.

The electronic device may be a memory device, a heater, a transistor, a temperature sensor, a strain sensor, an EMG sensor, an EEG sensor, or an integrated device including the same, but is not limited thereto.

FIG. 1 is a diagram showing a comprehensive health diagnosis / analysis / drug delivery system in the form of a patch and illustrates the use of electronic devices implemented on a patch in the case of a movement disorder. When a person wearing the patch-type electronic device exhibits a behavioral disorder, it is measured by a strain guage on the patch, and the measured data are stored in a wearable RRAM, and the stored data is analyzed. Pattern analysis enables a heater for feedback drug treatment (Feedback thermal actuation) and drug delivery through drug-filled mesoporous silica nanoparticles or biodegradable polymeric nanoparticles (Drug delivery).

The memory device may be an active memory device such as a DRAM, a flash memory, or a spin-torque-transfer RAM, or a passive memory device such as a resistive RAM, a phase change RAM, or a ferroelectric RAM.

The stretchable and flexible electronic device included in the wearable electronic device of the present invention includes an elastic substrate; A first patterned polymer layer formed adjacent said elastic substrate; An electronic device formed adjacent the patterned polymer layer; And a second patterned polymer layer formed adjacent to the memory device, wherein each of the first electrode and the second electrode of the memory device adjacent to the first patterned polymer layer and the second patterned polymer layer is patterned. It may be ized.

As used herein, the term “flexible and flexible electronic device” refers to an electronic device that exhibits a stable structure and operation even in deformation such as stretching, compression, bending, twisting, and the like.

The elastic substrate may be polydimethylsiloxane (PDMS), polyurethane, styrene-butadiene-styrene (SBS), epoxy resin or phenolic resin.

The first patterned polymer layer or the second patterned polymer layer may be selected from polyimide, benzocyclobutene or SU-8. As used herein, "SU-8" refers to an epoxy-based negative photoresist.

The first patterned polymer layer, the second patterned polymer layer, and the first patterned electrode and the second patterned electrode may be patterned in serpentine.

The electronic device included in the flexible and flexible electronic device of the present invention may be a memory device such as an active memory device or a passive memory device. The active memory device may be a DRAM, a flash memory, a spin-torque-transfer RAM (STT-RAM), or the like, and the passive memory device may be a resistance RAM. (RRAM)), Phase Change RAM (PCRAM), Ferroelectric RAM (FERAM), and the like.

In particular, the electronic device included in the stretchable and flexible electronic device of the present invention may be a nonvolatile resistive memory device. The nonvolatile resistive memory device includes: a first patterned electrode; An insulator layer made of a first metal oxide formed adjacent to the first electrode; A metal nanoparticle layer formed adjacent to the first metal oxide insulator layer; An insulator layer made of a second metal oxide formed adjacent to the metal nanoparticle layer; And a second patterned electrode formed adjacent to the second metal oxide layer.

In the nonvolatile resistive memory device, the first electrode may be selected from Al, Cu, Ag, Au, Pt, TiN, ITO, TaN, W, Mg, Zn, or Fe.

In addition, the first metal oxide may be selected from titanium dioxide, tantalum oxide, vanadium oxide, molybdenum oxide, aluminum oxide, cobalt oxide, zinc oxide, magnesium oxide, zirconium oxide, or hafnium oxide. The thickness of the first metal oxide insulator layer may be 5 nm to 200 nm.

In addition, the metal nanoparticles may be Au, Pt or Ag, the size of the metal nanoparticles may be 2 nm to 100 nm. The metal oxide nanoparticle layer may be formed by a Langmuir-blojet assembly, a layer-by-layer assembly, or a spin coating assembly process of nanoparticles. In addition, the number of the metal oxide nanoparticle layers can be from 1 to 10 layers, and can be adjusted to the required power. More preferably, the number of metal oxide nanoparticle layers may be three layers.

As used herein, "langmuir-blojet assembly" refers to a two-dimensional layer of nanoparticles by dipping a solid substrate into a liquid and then removing and transferring one or more nanoparticle monolayers from the subphase of the liquid onto the solid substrate. It means to form.

As used herein, "self-assembly" refers to the process by which a disordered system of components forms an organized structure or pattern as a result of certain local interactions between the components.

The second metal oxide of the nonvolatile memory device may be selected from titanium dioxide, tantalum oxide, vanadium oxide, molybdenum oxide, aluminum oxide, cobalt oxide, zinc oxide, magnesium oxide, zirconium oxide, or hafnium oxide. The thickness of the second metal oxide insulator layer may be 5 nm to 200 nm.

In addition, the second patterned electrode may be selected from Al, Cu, Ag, Au, Pt, TiN, ITO, TaN, W, Mg, Zn or Fe.

2A and 2B show a single crystal silicon nanomembrane (about 80 nm) strain sensor, a temperature sensor, a TiO ₂ nanomembrane (about 66 nm) RRAM array, and an electroresistive heater. shows a wearable electronic device including a heater. This versatile array of sensors and memories is transcribed onto an elastic hydrocolloid patch (Derma-Touch, Kwang-Dong Pharmaceutical, Korea). To minimize bending-induced strain, a switching layer of TiO ₂ nanomembrane containing gold nanoparticles is formed between the same polyimide layers (about 1.2 μm) to form a neutral mechanical plane ( Above the upper left side of FIG. 2A). Further control of the thickness of the inorganic active layer on the order of tens of nanometers further reduces flexural rigidity and induced strain. The mesoporous silica nanoparticles filled with the therapeutic drug are transcribed onto the hydrocolloid side of the dermal patch (lower middle in FIG. 2A). Very thin twisty wires and low modulus hydrocolloids together provide good mechanical contact with the skin. The inset of FIG. 2B is an enlargement of a 10 × 10 RRAM array in a serpentine network, which is integrated with a sensor transmitting an analog output. The drug filled in the mesoporous silica nanoparticles diffuses into the dermis, and the diffusion rate is controlled by the temperature of the hydrocolloid elastomer controlled by the heater. The temperature sensor warns of skin burns by providing temperature feedback on the spot.

Another object of the present invention can be achieved by providing a method for manufacturing a wearable electronic device, comprising attaching the stretchable and flexible electronic device to a biocompatible film that is adhereable to the skin.

In the method of manufacturing the wearable electronic device, the biocompatible film may be a polyurethane film coated with a hydrocolloid adhesive.

In addition, the hydrocolloid pressure-sensitive adhesive in the biocompatible film may be included, drug-filled mesoporous silica nanoparticles or biodegradable polymer nanoparticles. While the drug filled in the mesoporous silica nanoparticles is released, it can be absorbed by the human body through the skin.

Still another object of the present invention is to (i) coating and curing poly (methyl methacrylate) and the first polymer on a silicon substrate in turn; (ii) patterning the first polymer layer; (iii) fabricating an electronic device adjacent to the first patterned polymer layer; (iv) forming a second patterned polymer layer adjacent the electronic device; (v) removing the silicon substrate and the poly (methyl methacrylate) to obtain a device encapsulated with the first polymer and the second polymer; (vi) removing the poly (methyl methacrylate) layer from the device encapsulated with the first polymer and the second polymer and attaching to the elastic substrate; And (vii) attaching the device having the poly (methyl methacrylate) layer removed from the elastic substrate to a biocompatible film attachable to the skin, wherein the first patterned polymer layer and the second patterned It can be achieved by providing a method of manufacturing a wearable electronic device, wherein each of the first electrode and the second electrode of the electronic device adjacent to the polymer layer is patterned.

In the method for manufacturing the wearable electronic device, the elastic substrate may be polydimethylsiloxane, polyurethane, styrene-butadiene-styrene (SBS), epoxy resin or phenol resin.

In addition, the first polymer layer or the second polymer layer may be selected from polyimide, benzocyclobutene (BCB) or SU-8.

In addition, the electronic device may be selected from a memory device, a heater, a transistor, a temperature sensor, a strain sensor, an EMG sensor, an EEG sensor, or an integrated device including the same.

The electronic device may be a memory device such as an active memory device or a passive memory device. The active memory device may be a DRAM, a flash memory, a spin-torque-transfer RAM (STT-RAM), or the like, and the passive memory device may be a resistance RAM. (RRAM)), Phase Change RAM (PCRAM), Ferroelectric RAM (FERAM), and the like.

In particular, the electronic device may be a nonvolatile resistive memory device. Further, the nonvolatile resistive memory element may include a first patterned electrode; An insulator layer made of a first metal oxide formed adjacent to the first electrode; A metal nanoparticle layer formed adjacent to the first metal oxide insulator layer; An insulator layer made of a second metal oxide formed adjacent to the metal nanoparticle layer; And a second patterned electrode formed adjacent to the second metal oxide layer.

In addition, the hydrocolloid pressure-sensitive adhesive in the biocompatible film may be included, drug-filled mesoporous silica nanoparticles or biodegradable polymer nanoparticles.

According to the present invention, by implementing an integrated medical electronic device on a very thin and light skin patch, it is possible to perform a medical examination without inconvenience in daily life. In addition, since the present invention can implement an integrated system for drugs or additional treatment, it can be effectively applied to the treatment of diseases that require continuous observation in daily life.

1 illustrates one embodiment of a wearable electronic device of the present invention.

FIG. 2 is a wearable memory array including TiO ₂ nanomembrane (NM) -Au nanoparticles (NPs) —TiO ₂ NM switching layer and an Al electrode in a wearable electronic device manufactured in Embodiment 2 of the present invention. 2a, the top left view shows the layer information), a picture of the wearable system corresponding to FIG. 2a (FIG. 2b).

3A is a diagram illustrating Langmuir-Blodge (LB) assembly and stearic acid (SAM) functionalization; 3b are photographs (top) for the LB assembly process and planar TEM photographs (bottom) for single layer gold nanoparticles and three layer gold nanoparticles; 3C is cross-sectional TEM photographs of fabricated memory cells; 3D is an EDS profile showing the thickness of three layer gold nanoparticles in MINIM (Metal-Insulator-Nanoparticle-Insulator-Metal).

4A shows, in Example 3 of the present invention, MIM (Metal-Insulator-Metal), MISIM (Metal-Insulator-Self-Assembly Monolayer (SAM) -Insulator-Metal) and MINIM attached to PDMS and encapsulated with polyimide Showing the IV characteristics of the bipolar resistive switching of the structures; 4B is a diagram illustrating low current resistive switching due to Au nanoparticle-induced traps; 4C is an I-V curve in MIM and MINIM attached to PDMS and encapsulated with polyimide; 4D shows I-V characteristics at compliance currents up to about 100 μA in MIM and MINIM attached to PDMS and encapsulated with polyimide; 4E is a result of reliability test (durability (left) and retention (right)) of MINIM attached to PDMS and encapsulated with polyimide (resistance measurement at -0.5 V); 4F is the cumulative probability in MIM and MINIM attached to PDMS and encapsulated with polyimide; 4G shows MLC (multilayer cell) operation in MIM (left) and MINIM (right) attached to PDMS and encapsulated with polyimide.

FIG. 5 is a micrograph (FIG. 5A) in which stretch and soft memory devices are stretched by about 25% in Example 4 of the present invention, each with a different strain value (3% -25%). Skin-compatible memory on the wrist, showing the IV characteristics of the stretchable and flexible memory device (FIG. 5B), and the stretch and soft resistance memory arrangement in the bent state (FIG. 5C left) and in the twisted state (FIG. 5C right). In the device (first frame from the left in FIG. 5D), without deformation (second frame from the left in FIG. 5D), in the compressed state diagram (the third frame from the left in 5D) and in the tension state (last frame from the left in FIG. 5D). Show magnification, show simulation results for strain distribution in stretched RRAM (FIG. 5E), show change in resistance (HRS and LRS) at -0.5 V over 1,000 stretch cycles (about 30%). (FIG. 5F), waterproof in PBS (left of FIG. 5G) and read It illustrates the flow (Fig. 5g right).

6A is a schematic diagram illustrating a transfer printing process of drug-filled mesoporous silica nanoparticles, a sensor and a memory device, and FIG. 6B is a photograph of a structured PDMS stamp used in the transfer printing process.

FIG. 7A is a photograph of a silicon nanomembrane sensor (insertion shows the silicon nanomembrane doped with boron), FIG. 7B is the percent change in resistance versus strain plot to calculate the gauge factor, and FIG. 7C Deformation measurement picture on the wrist in tension and compression state, FIG. 7D shows resistance change over time (top), memory in silicon strain gauge caused by hand shake simulated at frequencies of 0.8, 0.4, 0.6 and 1 Hz The MLC operation of the cell (middle) and the data written to the MINIM memory cell (bottom).

FIG. 8A is a schematic diagram of controlled transdermal drug delivery from hydrocolloid and mesoporous silica nanoparticles by thermal action, FIG. 8B shows measurement of the temperature distribution of the heater on the skin patch using an infrared camera, FIG. 8C 3D thermal profile at the interface between the heater on the patch and the patch and human skin, FIG. 8D is a high resolution camera photograph (insertion micrograph) of mesoporous silica nanoparticles, and FIG. 8E is mesoporous TEM picture of silica nanoparticles, FIG. 8F shows the surface area calculated from the adsorption and desorption measurements of N2 at 77K (insertivity calculated using the Barrett-Joyner-Halenda (BJH) method, mesoporous silica nanoparticles 8g shows the above surface of the heater (red), the interface between the skin and the patch (orange) and the absence of heating. (Black) shows the maximum temperature as a function of time, the y-axis on the right shows that the diffusion coefficient increases exponentially with increasing temperature (blue in FIG. 8g), and FIG. 8h is the characteristic curve of the temperature sensor, FIG. 8I is a fluorescence photograph of the cross section of porcine skin after diffusion of rhodamine B fluorescent dye at 25 ° C. (top) and 40 ° C. (bottom) for 5 minutes (left) and 60 minutes (right).

FIG. 9 is a packaging test result for corrosion or degradation due to sweat when the RRAM memory module operates on the skin. The left photo of FIG. 9 shows evaluation of whether memory operation is stable when Phosphate Buffered Saline (PBS) solution is applied to an RRAM array on a PDMS substrate. The data in the right figure of FIG. 9 shows whether the memory programmed at -0.5V is well stored. No data is lost for 60 seconds, demonstrating good RRAM memory array packaging.

Hereinafter, the present invention will be described in more detail with reference to the following examples or drawings. However, the following description of the embodiments or drawings is only intended to specifically describe the specific embodiments of the present invention, it is not intended to limit or limit the scope of the present invention to the contents described therein.

실시예 1. 금 나노입자의 합성Example 1 Synthesis of Gold Nanoparticles

0.4 g of HAuCl ₄ .3H ₂ O (99.9%, Strem, USA), oleylamine (90%, Acros, USA) and 30 mL of 1-octadecene (90%, Sigma Aldrich, USA) at room temperature 50 Mix in mL glass vials. The vial was placed in an oil bath and heated to 90 ° C. The solution was heated for 2 hours, after which nanoparticles were precipitated and washed twice with ethanol and then centrifuged. The precipitated nanoparticles were redispersed in 5 mL of chloroform.

Example 2 Fabrication of Wearable Electronic Device Including Nonvolatile Resistance Change Memory Device

Poly (methyl methacrylate) (PMMA) (A11, Microchem, USA; spin coated at about 1 μm for 30 seconds at 3000 rpm) and polyimide (PI) (polyamic acid, Sigma Aldrich, USA; about 1.2 μm, 4000 Thin layers of precursor solution of spin coated at rpm for 60 seconds were spin coated onto a Si handle wafer (test grade, 4science, Korea). After the PMMA and PI were cured at 200 ° C. for 2 hours, aluminum used as the first electrode was deposited by thermal evaporation (350 nm thick), patterned by photolithography and wet etching was performed. Thereafter, first TiO ₂ nanomembrane (thickness 66 nm) was subjected to RF magnetron sputtering (base pressure 5 × 10 ⁻⁶ Torr, room temperature, deposition pressure 5 mTorr, 20 sccm, RF Power 150 W) (first metal oxide insulator layer).

As follows, the gold nanoparticles synthesized in Example 1 were assembled on the first TiO ₂ nanomembrane through a Langmuir-Bloze assembly process (FIG. 3A). First, gold nanoparticles capped with oleylamine were dispersed in chloroform (50 mg / mL). The dispersion was added dropwise onto a water sub-phase of an LB trough (LB trough; IUD 1000, KSV instrument, Finland). After evaporating the solvent, the surface layer was compressed using a mobile barrier (5 mm / min). After the surface pressure reached 30 mN / m, the gold nanoparticle layer was assembled on the substrate by lifting the substrate and soaking at a rate of 1 mm / min.

3B shows photographs (top) of the LB assembly process and planar TEM photographs (bottom) of one layer of gold nanoparticles and three layers of gold nanoparticles. The number of assembly layers can be controlled by the number of dipping / pulling cycles. Instead of a gold nanoparticle layer, the first TiO ₂ nanomembrane was coated with a self-assembled monolayer (stearic acid) to confirm the ligand effect on memory performance (FIG. 3A). i) a metal-insulator-self-assembled monolayer (SAM) -insulator-metal (MISIM), ii) a metal-insulator-nanoparticle (NP) -insulator- comprising a layer of gold nanoparticles (about 12 nm) Metal (MINIM), iii) MINIM comprising three layers of closely-packed gold nanoparticles (about 26 nm) is shown in FIG. 3C. The thickness of the gold nanoparticle layer of the three layers was confirmed through an energy dispersive X-ray specroscopy profile for the cross section (FIG. 3D). In the LB assembly method, closely-packed monolayer assembly plays an important role in device uniformity as well as accurate thickness control of several monolayers.

Then, using the same method as the deposition of the TiO ₂ nano-membrane of claim 1, it was deposited to a second TiO ₂ nano-membrane (second non-conductive metal oxide layer) on the gold nanoparticle layer (66 nm thick). An aluminum second electrode was deposited adjacent to the second TiO ₂ nanomembrane by thermal deposition. The second electrode layer was patterned by a photolithography method to produce a serpentine-patterned resistance memory. Next, the PI precursor was spin-coated to form the active layer near the neutral mechanical plane, and a reactive ion etching (RIE) process using O ₂ and SF ₆ was performed. ₂ flow rate 100 sccm, chamber pressure 100 mTorr, 150 W RF power, 5 minutes; SF ₆ flow rate 50 sccm, chamber pressure 55 mTorr, 250 W RF power, 4 minutes 30 seconds) to form the entire device structure.

After fabrication of the memory device, the entire device on a silicon wafer was immersed in boiling acetone. The acetone removed the PMMA layer to separate the PI encapsulated device from the silicon handle wafer. Thereafter, the memory device was separated using a water-soluble tape (3M, USA), and then transferred onto a printed polydimethyl siloxane (PDMS), and then again a skin patch (Derma-Touch, Kwang Dong Pharmaceutical Co., Ltd., Korea) Moved up. Electrical measurements were performed using a parameter analyzer (B1500A, Agilent, USA).

실시예 3. 비휘발성 저항 변화 메모리 소자의 특성 평가Example 3 Characterization of Nonvolatile Resistance Change Memory Device

To evaluate the electrical performance, bipolar IV curves were obtained for MIM, MISIM and MINIM structures attached to PDMS and encapsulated with polyimide, prepared according to the method of Example 2 (FIG. 4A). ). 4A shows the bias order. The initial state is a high-resistance state (HRS), and transitions to a low-resistance state (LRS) by applying a negative voltage (“set”). The structures are then switched to HRS by a positive voltage ("reset"). The I-V properties of MIM and MISIM attached to PDMS and encapsulated with polyimide were nearly identical; Forming one gold nanoparticle layer in the TiO 2 layer reduced the set and reset currents by an order of magnitude compared to the MIM structure. The level of the current was further reduced by an order of three in MIMIN comprising three gold nanoparticle layers. These results indicate that the assembly of uniform gold nanoparticles in the active layer plays an important role in the reduction of power consumption, and the stearic acid ligand has little effect on the current reduction. These low power consumption characteristics play an important role in long-term use of the memory device.

4B is a diagram showing low current switching due to gold nanoparticle-induced traps. 4C is a log-log I-V curve highlighting the negative voltage region. The conduction mechanism in MINIM attached to PDMS and encapsulated with polyimide is similar to the conduction mechanism of MIM, and the trap-controlled space-charge-limited-current (SCLC) theory Follow. 4D shows I-V curves at different compliance currents for MIM (left) and MINIM (right) attached to PDMS and encapsulated with polyimide. At compliance currents of 100 μA or less, MINIM attached to PDMS and encapsulated with polyimide showed better on / off ratio than MIM and MISIM attached to PDMS and encapsulated with polyimide. Reliability (endurance and retention) of MINIM, MIM and MISIM attached to PDMS and encapsulated with polyimide are shown in FIG. 4E, respectively. In the continuous sweep over 100 cycles, durability showed little degradation (Figure 4E left), and a good retention rate of 1,000 seconds at room temperature was confirmed (Figure 4E right). Multi-level cell (MLC) operation means that multiple data storage is possible in a single cell with discrete compliance currents that have discrete resistance values (FIG. 4D). Such different resistance values allow multiple information to be stored in a single cell (FIG. 4G). MLCs with current values below -100 μA were performed in MINIM attached to PDMS and encapsulated with polyimide, and data was preserved in more than 100 read operations.

실시예 4. 신축성 및 연성 저항 메모리 소자의 기계적 안정성Example 4 Mechanical Stability of Flexible and Flexible Resistance Memory Devices

Optical micrographs and stretching characteristics of the stretchable and flexible resistive memory devices manufactured in Example 2 are shown in FIGS. 5A and 5B, respectively. When the device was stretched by about 25% (the strain limit of the human epidermis was about 20%), the device showed stable electrochemical operation. The stretchable and flexible resistive memory device was stable even in bending and twisting (FIG. 5C). In addition, in Example 2, the wearable electronic device manufactured from the stretchable and flexible resistance memory device was modified in conformity with human skin (FIG. 5D). FIG. 5E shows the results of finite element modeling (FEM) on the strain distribution of the active layer (TiO ₂ nanomembrane). By placing nanometer-thick membranes and nanoparticles on the neutral dynamic layer and adopting a serpentine design, the induced strain is maintained below 0.1% in the switching layer and the tortuous The serpentine interconnects remained below 0.05%. The skin-adaptive memory showed minimal signal reduction even after 1,000 stretch cycles (about 30% strain, FIG. 5F). Figure 5g shows a photograph of the memory device in phosphate buffered saline (left) and no significant current change (right), indicating that the encapsulation layer can block perspiration uptake.

실시예 5. 메조기공성(mesoporous) 실리카 나노입자의 합성Example 5 Synthesis of Mesoporous Silica Nanoparticles

NaOH (0.35 mL, 2M, 98%, Sigma-Aldrich, USA) was added to 50 mL of cetyltrimethylammonium bromide (CTAB,> 99%, Acros, USA) solution (100 mg dissolved in 50 mL of water). . The mixture was heated to 70 ° C. and then 0.5 mL of tetraethylorthosilicate (TEOS, 98%, Acros, USA) was added. After 1 minute, 0.5 mL of ethyl acetate (99.5%, Samchun, Korea) was added and the resulting mixture was stirred at 70 ° C. for 30 seconds and then aged for 2 hours. The precipitate thus obtained was collected by centrifugation and washed with a large amount of water and ethanol. Finally, mesoporous silica (m-silica) nanoparticles were prepared by removing the pore-generating template, CTAB, by reflux in acidic ethanol solution.

Example 6 Rhodamine B Fluorescent Dye Stuffed with Mesoporous Silica Nanoparticles

As a drug diffusion model, rhodamine B (≧ 95%, Sigma-Aldrich, USA) was charged to mesoporous silica nanoparticles. Rhodamine B solution (0.2 mL, 20 mg / mL in methanol) was adsorbed onto the surface of the mesoporous silica nanoparticles (0.15 g). Rhodamine B packed in the mesoporous silica nanoparticles was dried at room temperature.

Example 7 Fabrication of Structured PDMS Stamp for Transcription Printing on Drug-Filled Mesoporous Silica Nanoparticles

Negative photoresist (SU8-25, Microchem, USA) was precleaned and spin coated onto silicon wafers treated with O ₂ plasma. Photolithography was performed on the spin-coated SU8 to pattern holes 40 μm deep, 600 μm wide and 1.46 nm apart. The SU8 mold was then placed on a heated dish on a plate at 150 ° C. to promote adhesion between the mold and the silicon wafer. 10: 1 PDMS (Sylgard 184A: Sylgard 184B, Dow Corning, USA) was poured into the dish. After 24 hours, the cured structured PDMS and micro-dot array were slowly removed from the SU8 mold (FIG. 6B).

Example 8 Transcription Printing Over Skin Patches of Drug-Filled Mesoporous Silica Nanoparticles

Drug filled (or dye filled) mesoporous silica nanoparticle solutions were dropped onto the structured PDMS stamp. The stamp was dried for about 20 minutes. The dried dye-filled mesoporous silica nanoparticles were transferred and printed onto the hydrocolloid side of the skin patch as a microdot array (FIG. 6A).

실시예 9. 적외선 카메라를 사용한 히터의 온도 분포 측정Example 9 Measurement of Temperature Distribution of Heater Using Infrared Camera

Wavy-patterned Cr / Au-based heaters (10 nm / 190 nm, line width 300 μm, 95.9 Ω) on a 1 mm thick slide glass were supplied at an ambient temperature of 15 ° C. (12 V, 1.5 W). An infrared camera (320 × 240 pixels, IRE Korea, Korea) was used to capture time-dependent thermo-grams and the maximum temperature of the heater was shown.

Example 10 Fabrication of Single Crystal Silica Nanomembrane Strain Sensors on Skin Patches

The fabrication process was started with spin coating PMMA and PI on the silicon wafer. 80 nm by photolithography and RIE (SF ₆ plasma, 50 sccm, chamber pressure 50 mTorr) process of silicon-on-insulator (SOI) wafers doped with boron (doping concentration: about 9.7 × 10 ¹⁸ / cm ³ ) A silicon nanomembrane of thickness was formed, which was transferred and printed on the PI film. Thermal evaporation was used for the subsequent metallization (Cr / Au, 7 nm / 70 nm thick), after which the metal film was formed as a specific pattern by photolithography and wet chemical etching. Next, the top PI layer was covered and all three layers (PI / device / PI) were patterned and etched by O ₂ and SF ₆ RIE. The entire device was removed from the silicon wafer by removing the PMMA sacrificial layer using acetone. The detached device was transferred to a skin patch.

7A shows an arrangement of stretchable strain sensors based on silicon nanomembrane (inset), as a typical example of a wearable sensor adjacent to a collocated memory. The strain gauge has an effective guage factor of about 0.5. Due to the very thin serpentine interconnect, the sensors adhered well to the skin even during repeated exposure to tension and compression in the human wrist (FIG. 7C). This specific example mimics a shaking mode that causes hand frequencies of different frequencies, as seen in epilepsy and Parkinson's disease (FIG. 7D). The other tremor frequency serves as the main tracking factor for monitoring and diagnosing these movement disorders. Representative frequencies corresponding to different frequency bands (0.-0.5, 0.5-0.7, 0.7-0.9 and> 0.9 Hz) are based on four different levels (Fig. 7D) based on the MLC operation of the MINIM wearable memory (Fig. 4G). As shown below).

실시예 11. 피부 패치 상에서 전기저항성 히터/온도 센서 제작Example 11. Fabrication of Electric Resistance Heater / Temperature Sensor on Skin Patch

A skin-mountable heater was fabricated by thermal evaporation of Cr / Au (10 nm / 190 nm thickness) through a metal mask of a tortuous shape to produce a non-tacky surface (hydrocolloid ( A serpentine shape was formed on the opposite side of the hydrocolloid) After the wiring, the heater was wrapped with PDMS film The same design and fabrication method can be used for the temperature sensor.

실시예 12. 데이터 처리 및 저장 시스템Example 12. Data Processing and Storage System

By capturing a physiological strain signal using the onboard sensor, the sensing and data storage steps can be initiated and stored locally in the cells of the nonvolatile memory. For this system, a custom program written in Lab View software (National Instruments, USA) was used to process and store the recorded data. For example, in the case of strain detection for a tremor model in motion-related neurological disorders (FIG. 7D), the tremor recorded by the mounted strain gauge Frequency was analyzed and classified into four different bands (0-0.5, 0.5-0.7, 0.7-0.9, and> 0.9 Hz) by the customized Lab View program. Under MLC operation through a probe station, the program determines the appropriate compliance current and bias voltage to determine two specific digit codes ([00], [01], [10], and [11]. , Which are pre-assigned for each band) were written to the mounted wearable memory cell.

An application for sensing and data storage is to use the stored information to trigger treatment initiation. One possible mode of use is to feed the recorded data through a control circuit that recognizes the characteristic pattern of the disease and then trigger / control drug release (FIG. 8A). We used mesoporous silica nanoparticles as the vehicle containing and delivering the drug (FIGS. 8D-8F), and the diffusion promoting / temperature monitoring devices (FIGS. 8B, 8C 8G and 8H) for controlled transdermal drug delivery. An electroresistive heater / temperature sensor was used as () (FIG. 8I). Drug-filled mesoporous silica nanoparticles were transferred-printed onto the tacky side of the patch using a structured polydimethylsiloxane (PDMS) stamp. Mesoporous silica nanoparticles containing nanopores (FIG. 8E) have a very large surface area for drug adsorption (FIG. 8F). 8B shows a thermal gradient photograph (infrared camera measurement) for an electrically resistive heater on the patch surface. 8C shows the corresponding FEM analysis results highlighting the three-dimensional thermal profile for the device on the multilayered human skin, demonstrating that sufficient heat is transferred to the skin and the nanoparticles. The heat generated by the heater breaks the physical bond between the nanoparticles and the drug so that the drug filled in the nanoparticles is percutaneously diffused. As a result of the FEM simulation, it was confirmed that the diffusion rate was increased by heating (FIG. 8G). The temperature sensor (FIG. 8H) can monitor the maximum temperature (<43 ° C.) that can prevent skin burns. Percutaneous drug delivery can be visualized by fluorescence micrographs of the diffusion of dye (rhodamine B) into pig skin at room temperature (25 ° C., FIG. 8i) and at elevated temperature (40 ° C., FIG. 8i). . The depth at which the dye penetrated the pig skin at room temperature was shallower than the depth of penetration at elevated temperatures, which means that diffusion accelerated by thermal action.

실시예 13. 패치 위에 설치된 전자 기기들의 패키징 성능 분석Example 13 Analysis of Packaging Performance of Electronic Devices Installed on a Patch

Electronic devices should be packaged to prevent malfunctions caused by foreign substances such as sweat emitted from human skin or external water. The electronic devices fabricated by the method of Example 3 are well protected by an encapsulation layer, so that performance is hardly changed by stimulation of external materials such as sweat. As shown in FIG. 9, when the 1 M PBS (Phosphate Buffered Saline Solution) solution having a much higher concentration of ions than sweat was dropped on the electronic device, it was observed that the electronic device works well.

Claims

A wearable electronic device comprising a biocompatible film adhesive to the skin and stretchable and flexible electronic devices attached to the biocompatible film.
The wearable electronic device of claim 1, wherein the biocompatible film is a polyurethane film coated with a hydrocolloid adhesive.
The wearable electronic device as claimed in claim 1, wherein drug-filled mesoporous silica nanoparticles or biodegradable polymer nanoparticles are included on a surface to which a hydrocolloid adhesive is applied in the biocompatible film.
The wearable electronic device of claim 1, wherein the electronic device is at least one selected from the group consisting of a memory device, a heater, a transistor, a temperature sensor, a strain sensor, an EMG sensor, an EEG sensor, and an integrated device including the same. .
The wearable electronic device of claim 4, wherein the memory device is a nonvolatile memory device.
The flexible electronic device of claim 1, wherein the stretchable and flexible electronic device includes:

Elastic substrates;

A first patterned polymer layer formed adjacent said elastic substrate;

An electronic device formed adjacent the patterned polymer layer;

A second patterned polymer layer formed adjacent to the memory device,

Wherein the first electrode and the second electrode of the memory device adjacent to the first patterned polymer layer and the second patterned polymer layer are each patterned, a flexible and flexible electronic device.

Wearable electronic device.
The wearable electronic device of claim 6, wherein the elastic substrate is selected from the group consisting of polydimethylsiloxane, polyurethane, styrene-butadiene-styrene rubber, epoxy resin, and phenol resin.
The wearable electronic device of claim 6, wherein the first patterned polymer layer or the second patterned polymer layer is selected from the group consisting of polyimide, benzocyclobutene and SU-8.
7. The method of claim 6, wherein the first patterned polymer layer, the second patterned polymer layer and the first patterned electrode and the second patterned electrode are patterned in serpentine. Wearable electronic device, characterized in that.
The wearable electronic device of claim 6, wherein the electronic device is an active memory device or a passive memory device.
The wearable electronic device of claim 10, wherein the active memory device is selected from the group consisting of DRAM, flash memory, and spin-torque-transfer RAM.
The wearable electronic device of claim 10, wherein the passive memory device is selected from the group consisting of a resistive ram, a phase change ram, and a ferroelectric ram.
The wearable electronic device of claim 6, wherein the electronic device is a nonvolatile resistive memory device.
The memory device of claim 13, wherein the nonvolatile memory device includes:

A first electrode;

An insulator layer made of a first metal oxide formed adjacent to the first electrode;

A metal nanoparticle layer formed adjacent to the first metal oxide insulator layer;

An insulator layer made of a second metal oxide formed adjacent to the metal nanoparticle layer; And

And a second electrode formed adjacent to the second metal oxide layer.

Wearable electronic device.
The wearable electronic device of claim 14, wherein the first electrode is selected from the group consisting of Al, Cu, Ag, Au, Pt, TiN, ITO, TaN, W, Mg, Zn, and Fe.
The method of claim 14, wherein the first metal oxide is selected from the group consisting of titanium dioxide, tantalum oxide, vanadium oxide, molybdenum oxide, aluminum oxide, cobalt oxide, zinc oxide, magnesium oxide, zirconium oxide and hafnium oxide. A wearable electronic device characterized by the above-mentioned.
15. The wearable electronic device of claim 14, wherein the thickness of the first metal oxide insulator layer is 5 nm to 200 nm.
15. The wearable electronic device of claim 14, wherein the metal nanoparticles are nanoparticles of a metal selected from the group consisting of Au, Pt, and Ag.
The wearable electronic device of claim 14, wherein the metal nanoparticles have a size of 2 nm to 100 nm.
15. The wearable electron of claim 14, wherein the metal oxide nanoparticle layer is formed by a process selected from the group consisting of Langmuir-blojet assembly, layer-by-layer assembly, and spin coating assembly of nanoparticles. device.
The wearable electronic device of claim 14, wherein the number of the metal oxide nanoparticle layers is in a range of 1 to 10 layers.
15. The method according to claim 14, wherein the second metal oxide is selected from the group consisting of titanium dioxide, tantalum oxide, vanadium oxide, molybdenum oxide, aluminum oxide, cobalt oxide, zinc oxide, magnesium oxide, zirconium oxide and hafnium oxide. A wearable electronic device characterized by the above-mentioned.
The wearable electronic device of claim 14, wherein the second metal oxide insulator layer has a thickness of about 5 nm to about 200 nm.
The wearable electronic device of claim 14, wherein the second electrode is selected from the group consisting of Al, Cu, Ag, Au, Pt, TiN, ITO, TaN, W, Mg, Zn, and Fe.
Attaching the stretchable and flexible electronic device to a biocompatible film attachable to the skin,

Method for manufacturing wearable electronic device.
27. The method of claim 25, wherein the biocompatible film is a polyurethane film coated with a hydrocolloid adhesive.
27. The method of claim 25, wherein the drug-filled mesoporous silica nanoparticles or biodegradable polymer nanoparticles are included on the surface to which the hydrocolloid adhesive is applied in the biocompatible film.
The wearable electronic device of claim 25, wherein the electronic device is at least one selected from the group consisting of a memory device, a heater, a transistor, a temperature sensor, a strain sensor, an EMG sensor, an EEG sensor, and an integrated device including the same. Manufacturing method.
27. The method of claim 25, wherein the memory device is a nonvolatile resistive memory device.
30. The method of claim 29, wherein the memory device is a nonvolatile resistive memory device.
(i) coating and curing the poly (methyl methacrylate) and the first polymer on a silicon substrate in turn;

(ii) patterning the first polymer layer;

(iii) fabricating an electronic device adjacent to the first patterned polymer layer;

(iv) forming a second patterned polymer layer adjacent the electronic device;

(v) removing the silicon substrate and the poly (methyl methacrylate) to obtain a device encapsulated with the first polymer and the second polymer;

(vi) removing the poly (methyl methacrylate) layer from the device encapsulated with the first polymer and the second polymer and attaching to the elastic substrate; And

(vii) attaching the device having the poly (methyl methacrylate) layer removed from the elastic substrate to a biocompatible film attachable to the skin,

Wherein each of the first electrode and the second electrode of the electronic device adjacent to the first patterned polymer layer and the second patterned polymer layer is patterned

Method for manufacturing wearable electronic device.
32. The method of claim 31, wherein the elastic substrate is selected from the group consisting of polydimethylsiloxane, polyurethane, styrene-butadiene-styrene rubber, epoxy resin, and phenolic resin.
32. The method of claim 31 wherein the first polymer layer or the second polymer layer is selected from the group consisting of polyimide, benzocyclobutene and SU-8.
32. The method of claim 31 wherein the first patterned polymer layer, the second patterned polymer layer and the first patterned electrode and the second patterned electrode are patterned in serpentine. Wearable electronic device manufacturing method characterized in that.
32. The method of claim 31, wherein the electronic device is at least one selected from the group consisting of a memory device, a heater, a transistor, a temperature sensor, and a strain sensor.
36. The method of claim 35, wherein the memory device is an active memory device selected from the group consisting of DRAM, flash memory, and spin-torque-transfer RAM.
36. The method of claim 35, wherein the memory device is a passive memory device selected from the group consisting of a resistive ram, a phase change ram, and a ferroelectric ram.
32. The method of claim 31, wherein the electronic device is a nonvolatile resistive memory device.
The memory device of claim 38, wherein the nonvolatile memory device includes:

A first patterned electrode;

An insulator layer made of a first metal oxide formed adjacent to the first electrode;

A metal nanoparticle layer formed adjacent to the first metal oxide insulator layer;

An insulator layer made of a second metal oxide formed adjacent to the metal nanoparticle layer; And

And a second patterned electrode formed adjacent to the second metal oxide layer.
32. The method of claim 31, wherein the biocompatible film is a polyurethane film coated with a hydrocolloid adhesive.
41. The method of claim 40, wherein the drug-filled mesoporous silica nanoparticles or biodegradable polymer nanoparticles are included on the surface to which the hydrocolloid adhesive is applied in the biocompatible film.