KR20210097444A - Bio Sensor - Google Patents

Abstract

The present invention relates to a biosensor. Specifically, the biosensor according to an embodiment of the present invention includes a substrate on which an adhesive is formed on one surface, a flexible electrode part formed on another surface of the substrate, and a glucose reaction part formed on the flexible electrode part, wherein the flexible electrode part includes a conductive polymer. An object of the present invention is to provide a wearable biosensor capable of minimizing electrode cracks that may occur due to movement or stretching of a user wearing the wearable biosensor.

Description

Bio Sensor

The present invention relates to a biosensor. More specifically, the present invention relates to a glucose sensor.

Glucose is a broad source of nutrients for most organisms, and as a component that performs basic roles in energy supply, carbon storage, biosynthesis, and carbon skeleton and cell wall formation, a glucose sensor that measures the concentration of glucose through potentiometric or current measurement research is being actively carried out.

Most studies of glucose sensors are based on the immobilization of enzymes such as glucose oxidase or glucose dehydrogenase that catalyze the oxidation of glucose to gluconolactone.

Such a glucose sensor can be divided into an invasive type that mainly measures glucose contained in blood and a non-invasive type that mainly measures glucose contained in saliva, sweat, and the like.

In the case of a non-invasive glucose sensor, it is attached to the human body to analyze and monitor a biological solution containing saliva or sweat. In this case, in the case of a wearable glucose sensor attached to the human body, selectivity and sensitivity, as well as body stability and mechanical flexibility, must be satisfied at the same time.

However, in the case of the conventional wearable glucose sensor, electrode cracks often occur due to the user's movement or elongation, and such electrode cracks may lead to malfunction of the glucose sensor. Therefore, in order to solve this problem, a wearable glucose sensor with improved stretching characteristics will be described below.

Laid-Open Patent Publication No. 10-2016-0066706 Laid-Open Patent Publication No. 10-2015-7019224

The present invention relates to a wearable biosensor that can be attached to the skin, and an object of the present invention is to provide a wearable biosensor capable of minimizing electrode cracks that may occur due to movement or stretching of a user wearing the wearable biosensor.

The present invention relates to a biosensor. Specifically, the biosensor according to an embodiment of the present invention includes a substrate having an adhesive formed on one side thereof, a flexible electrode unit formed on another side of the substrate, and a glucose reaction unit formed on the flexible electrode unit, wherein the The flexible electrode part includes a conductive polymer.

The wearable biosensor according to an embodiment of the present invention includes the electrode part emphasizing the stretch characteristic, so that when attached to the body, the degree of freedom of the user's motion and attachment position can be increased.

In addition, the wearable biosensor according to an embodiment of the present invention uses a conductive polymer having stretch characteristics as an electrode, thereby reducing the overall process and production cost.

1 is a cross-sectional view of a typical glucose sensor.
2 exemplarily shows the electrode arrangement of the glucose sensor electrode unit.
3 is a cross-sectional view of a glucose sensor according to an embodiment of the present invention.
4 shows a result of comparing elongation rates between a glucose sensor and another glucose sensor according to an embodiment of the present invention.

Specific structural or functional descriptions of the embodiments according to the concept of the present invention disclosed in this specification are only exemplified for the purpose of explaining the embodiments according to the concept of the present invention, and the embodiments according to the concept of the present invention are It may be implemented in various forms and is not limited to the embodiments described herein.

Since the embodiments according to the concept of the present invention may have various changes and may have various forms, the embodiments will be illustrated in the drawings and described in detail herein. However, this is not intended to limit the embodiments according to the concept of the present invention to specific disclosed forms, and includes all modifications, equivalents, or substitutes included in the spirit and scope of the present invention.

Terms such as first or second may be used to describe various elements, but the elements should not be limited by the terms. The above terms are used only for the purpose of distinguishing one element from another, for example, without departing from the scope of the inventive concept, a first element may be termed a second element and similarly a second element. A component may also be referred to as a first component.

When a component is referred to as being “connected” or “connected” to another component, it may be directly connected or connected to the other component, but it is understood that other components may exist in between. it should be On the other hand, when it is said that a certain element is "directly connected" or "directly connected" to another element, it should be understood that the other element does not exist in the middle. Other expressions describing the relationship between components, such as "between" and "immediately between" or "neighboring to" and "directly adjacent to", etc., should be interpreted similarly.

The terms used herein are used only to describe specific embodiments, and are not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly dictates otherwise. As used herein, terms such as “comprise” or “have” are intended to designate that a feature, number, step, operation, component, part, or combination thereof described herein is present, but one or more other features It is to be understood that it does not preclude the possibility of the presence or addition of numbers, steps, operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in a commonly used dictionary should be interpreted as having a meaning consistent with the meaning in the context of the related art, and should not be interpreted in an ideal or excessively formal meaning unless explicitly defined in the present specification. does not

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

A biosensor is a system that converts information into a recognizable useful signal, such as color, shape, and electrical signal, by using a biological element or mimicking a biological element when obtaining information from a measurement object.

The biosensor is composed of a sensor matrix made of a biosensing material or biomimetic sensing material that can selectively recognize a target material and a signal converter that transmits a signal generated during the reaction. As a sensor matrix, enzymes, antibodies, antigens, membranes, receptors, cells, tissues, microDNA, etc. are used, and as a signal conversion method, electrochemistry, color development, optics, fluorescence, piezoelectricity, etc. are used.

1 is a cross-sectional view of a typical glucose sensor.

Referring to FIG. 1 , a typical glucose sensor includes a substrate 10 , an electrode unit 20 , an electron transfer unit 30 , a glucose reaction unit 40 , an electrolyte supply layer 50 , a wiring unit 70 , and a temperature sensor. (100).

Before describing detailed components of a glucose sensor according to an embodiment of the present invention, the main content of the present invention will be first described.

The substrate 10 functions to provide a structural base of the components constituting the glucose sensor.

For example, the substrate 10 may be implemented in the form of a base film having a rigid material such as glass or having a flexible characteristic. When the substrate 10 is implemented to be flexible, examples of specific materials that can be applied to the base film include polyester-based resins such as polyethylene terephthalate, polyethylene isophthalate, polyethylene naphthalate, and polybutylene terephthalate; Cellulose resins, such as a diacetyl cellulose and a triacetyl cellulose; polycarbonate-based resin; acrylic resins such as polymethyl (meth)acrylate and polyethyl (meth)acrylate; styrenic resins such as polystyrene and acrylonitrile-styrene copolymer; polyolefin-based resins such as polyethylene, polypropylene, polyolefin having a cyclo-based or norbornene structure, and an ethylene-propylene copolymer; vinyl chloride-based resin; amide resins such as nylon and aromatic polyamide; imide-based resin; polyether sulfone-based resin; sulfone-based resins; polyether ether ketone resin; sulfide polyphenylene-based resin; vinyl alcohol-based resin; vinylidene chloride-based resin; vinyl butyral-based resin; allylate-based resin; polyoxymethylene-based resins; and a film composed of a thermoplastic resin such as an epoxy-based resin, and a film composed of a blend of the above-mentioned thermoplastic resins can also be used. In addition, a film made of a thermosetting resin or ultraviolet curable resin such as (meth)acrylic, urethane, acrylic urethane, epoxy, or silicone may be used. The thickness of such a transparent optical film may be appropriately determined, but in general, in consideration of workability such as strength and handling properties, thin layer properties, etc., it may be determined to be 1 to 500 μm, particularly preferably 1 to 300 μm, 5-200 micrometers is more preferable.

Such a base film may contain one or more suitable additives. Examples of additives include ultraviolet absorbers, antioxidants, lubricants, plasticizers, mold release agents, color inhibitors, flame retardants, nucleating agents, antistatic agents, pigments, colorants, and the like. The base film may have a structure including various functional layers such as a hard coating layer, an anti-reflection layer, and a gas barrier layer on one or both sides of the film, and the functional layer is not limited to the above, and includes various functional layers depending on the use can do.

In addition, if necessary, the base film may be surface-treated. Examples of such surface treatment include chemical treatment such as plasma treatment, corona treatment, dry treatment such as primer treatment, and alkali treatment including saponification treatment.

The electrode unit 20 includes a plurality of electrodes formed on the substrate 10 . The electrode unit 20 detects an electrical signal generated by a reaction between the substance constituting the glucose reaction unit 40 to be described later and glucose contained in the measurement target material. For example, the measurement target material may be human saliva, sweat, body fluid, blood, etc., but is not limited thereto.

For example, the electrode part 20 is not particularly limited as long as it is a conductive material. The electrode part 20 is, for example, gold (Au), silver (Ag), copper (Cu), platinum (Pt), titanium (Ti), nickel (Ni), tin (Ni), molybdenum (Mo), It may include one or more selected from the group consisting of cobalt (Co) and APC, or an alloy thereof. APC is an Ag-Pd-Cu alloy.

The electrode part 20 may be formed on the substrate 10 by screen printing, physical vapor deposition or etching, or attaching a tape.

The electron transfer unit 30 is formed on the electrode unit 20 and a partial region of the substrate 10 outside the electrode unit 20 . The electron transfer unit 30 is reduced by redox reaction with the enzyme reduced by reacting with glucose, and the electron transfer mediator in the reduced state thus formed generates a current on the surface of the electrode to which the oxidation potential is applied.

The electron transport unit 30 may include an electron transport medium, for example, the electron transport medium is hexaammineruthenium (III) chloride, potassium ferricyanide, potassium ferro Cyanide (potassium ferrocyanide), dimethyl ferrocene (DMF), ferricinium (ferricinium), ferrocene monocarboxylic acid (FCOOH), 7,7,8,8, -tetracyanoqui Nodimethane (7,7,8,8-tetracyanoquino-dimethane (TCNQ)), tetrathia fulvalene (TTF), nickellocene (Nc), N-methylacidinium (N- methyl acidinium (NMA+)), tetrathiatetracene (TTT), N-methylphenazinium (NMP+), hydroquinone, 3-dimethylaminobenzoic acid (3-dimethylaminobenzoic acid ( MBTHDMAB)), 3-methyl-2-benzothiozolinone hydrazone (3-methyl2-benzothiozolinone hydrazone), 2-methoxy-4-allylphenol (2-methoxy-4-allylphenol), 4-aminoantipyrine ( 4-aminoantipyrin (AAP)), dimethylaniline, 4-aminoantipyrene, 4-methoxynaphthol, 3,3',5,5'-tetramethylbenzidine ( 3,3',5,5'-tetramethyl benzidine (TMB)), 2,2-azino-di-[3-ethyl-benzthiazoline sulfonate] (2,2-azino-di-[3-ethyl- benzthiazoline sulfonate]), o-dianisidine, o-toluidine, 2,4-dichlorophenol (2,4-dichl orophenol), 4-aminophenazone, benzidine, Prussian blue, bipyridine-osmium complex compound, etc. may be used. In addition, the electron transport unit 30 may be used by mixing a metal-containing complex and thionine or a derivative thereof.

In an additional embodiment, the electron transfer unit 30 may serve to protect the electrode unit 20 . For example, the electron transfer unit 30 may have a structure in which an electrode protector that protects the electrode unit 20 and an electron transfer medium that functions to transmit electrons are mixed. Here, in order to protect the electrode, the electron transfer unit 30 may further include an electrode protection material.

For example, Prussian blue included in the electron transport unit 30 is a component that performs an electron transport function, and is a blue pigment containing iron(III) potassium hexacyanoferrate (II) as a main component, and has high oxidation properties. . If the electron transfer unit 30 containing Prussian blue is formed between the electrode unit 20 and the glucose reaction unit 40, the sensitivity of the electrode can be improved, but a metallic electrode located under the Prussian blue color. The portion 20 may be oxidized and corroded.

Accordingly, in an additional embodiment of the present invention to prevent oxidation of the electrode part 20 to protect the electrode, the electron transport unit 30 may further include an electrode protection material together with the electron transport medium. In a specific example, the electrode protection material may be carbon.

The glucose reaction unit 40 is formed on the electron transfer unit 30 and may include an oxidoreductase that is reduced by reacting with glucose contained in the measurement target material. Here, the reduced enzyme reacts with the electron transfer mediator of the electron transfer unit 30 to quantify glucose.

For example, the glucose reaction unit 40 is flavin adenine dinucleotide-glucose dehydrogenase (FAD-GDH), nicotinamide adenine dinucleotide-glucose dehydrogenase (nicotinamide adenine dinucleotide- glucose dehydrogenase, NAD-GDH), pyrroloquinoline quinone-glucose dehydrogenase (PQQ-GDH), and glucose oxidase (GOx).

A reaction in the glucose reaction unit 40 and a signal sensing principle of the electrode unit 20 will be exemplarily described as follows.

[Scheme 1]

(1) Glucose + GOx-FAD → Gluconic acid + GOx-FADH- ₂

(2) GOx-FADH ₂ + electron transport mediator (oxidized state) → GOx-FAD + electron transport mediator (reduced state)

In Scheme 1, GOx represents glucose oxidase, and GOx-FAD and GOx-FADH ₂ represent the oxidation state and reduction state of flavin adenine dinucleotide (FAD), which is an active site of glycooxidase, respectively.

As shown in Scheme 1, (1) first, glucose in blood is oxidized to gluconic acid by the catalytic action of glycooxidase. At this time, FAD, the active site of glycooxidase, is reduced to FADH ₂ . (2) After the reduction is FADH ₂ FADH ₂ by the oxidation-reduction reaction with the electron transfer mediator is oxidized to the FAD, the electron transfer mediator is reduced.

The electron transport medium in the reduced state thus formed diffuses to the electrode surface. At this time, the current generated by applying the oxidation potential of the electron transport medium in the reduced state to the surface of the working electrode is measured. Since the concentration of glucose in the sample is proportional to the amount of current generated in the process of oxidation of the electron transport medium, the glucose concentration can be calculated by measuring the amount of current.

The electrolyte supply layer 50 is formed on the glucose reaction unit 40 . Materials included in the sample are not only glucose, but may contain various electrolytes. Specifically, electrolytes contained in the body include Na+, Cl-, NH4+, K+, Mg2+, Ca2+, and the like, and these ions need to be removed because they cause noise when measuring glucose.

Accordingly, the electrolyte supply layer 50 according to an embodiment of the present invention may include an electrolyte. And the electrolyte supply layer may include at least one of a cation or an anion.

The cations included in the electrolyte supply layer according to an embodiment of the present invention include a strongly acidic sulfonic acid group (-SO3-), a phosphoric acid group (-PO3-), a weakly acidic carboxylic acid group (-COO-) or Nafion. can be used

In addition, as the anion supplied to the electrolyte according to an embodiment of the present invention, a strongly basic quaternary ammonium group (-NR3+) is mainly used, and in specific examples of use, PPG-bis(2-aminopropyl ether)Mn4000 and PPG-bis(2 -aminopropyl ether)Mn230 and TMP-PPG-amine ether can be used.

As a result, since the electrolyte supply layer contains both positive and negative ions, the accuracy of the sensor can be improved by removing both the positive and negative electrolytes contained in the body fluid.

2 exemplarily shows an electrode arrangement of a glucose sensor electrode unit according to an embodiment of the present invention.

As illustrated in FIG. 2 , the electrode unit 20 may include a plurality of electrodes. The plurality of electrodes may include at least one working electrode 21-1 and 22-1 and at least one reference electrode 21-2 and 22-2. In addition, the working electrodes 21-1 and 22-1 and the reference electrodes 21-2 and 22-2 may be disposed to correspond to each other.

The plurality of poles constituting the electrode part 20 are gold (Au), silver (Ag), copper (Cu), platinum (Pt), titanium (Ti), nickel (Ni), tin (Ni), and molybdenum (Mo). ), cobalt (Co), may include one or more selected from the group consisting of APC, or an alloy thereof. APC is an Ag-Pd-Cu alloy.

In addition, the temperature sensor 100 for measuring the temperature of the glucose concentration measurement environment together with the electrode unit 20 may be formed on the substrate 10 .

In addition, the plurality of electrodes and the temperature sensor 100 may be connected to a glucose concentration calculating unit (not shown) through the wiring unit 70 .

The wiring unit 70 includes electrodes constituting the electrode unit 20 and a plurality of electrical wirings extending from the temperature sensor 100 . The wiring unit 70 may be connected to a sensing/analyzing means performing a current analysis function through an electrical connection medium such as a flexible printed circuit board (FPCB) (not shown). Although not shown in the drawing, a pad region may be provided at the end of the wiring unit 70 , and the FPCB may be attached to the pad region to be electrically connected.

The temperature sensor 100 is formed on the substrate 10 to measure the temperature of the environment in which the glucose concentration is measured. The temperature sensor 100 may sense the temperature of the glucose concentration measurement environment and transmit it to the glucose concentration calculating unit. Here, the glucose concentration calculation unit is ASICs (application specific integrated circuits), DSPs (digital signal processors), DSPDs (digital signal processing devices), PLDs (programmable logic devices), FPGAs (field programmable gate arrays, processors, controllers ( controllers), micro-controllers, microprocessors, and other electrical units for performing functions.

The glucose concentration calculating unit may consider the temperature transmitted from the temperature sensor 100 while calculating the glucose concentration based on the amount of current transmitted from the electrode unit 20 . In a specific embodiment, since the measured glucose concentration may have a deviation depending on the temperature, the calculated glucose concentration may be corrected according to the temperature. For example, the correction of the glucose concentration may be performed through a table of correction values according to a preset temperature.

3 is a cross-sectional view of a glucose sensor according to an embodiment of the present invention.

As shown in FIG. 3 , the glucose sensor 200 according to an embodiment of the present invention includes a substrate 210 , an adhesive unit 220 , a flexible electrode unit 230 , a glucose reaction unit 240 , and an ion exchange membrane ( 250). Additionally, the glucose sensor according to an embodiment of the present invention may further include the above-described wiring unit 70 and the temperature sensor 100 .

Here, the description of the substrate 210 , the glucose reaction unit 240 , and the electrolyte supply layer 250 is the same as the description of the substrate 10 , the glucose reaction unit 40 and the electrolyte supply layer 50 of FIG. 1 . Therefore, the description is omitted.

In this case, the adhesive part 220 may be attached to the lower surface of the substrate 210 . Specifically, in order for the wearable glucose sensor to be well attached to the user's skin, an adhesive portion may be formed on the body skin adhesion surface of the substrate 210 .

For example, the adhesive part 220 may have an elastic modulus of 0.01 to 100 Mpa at 25°C. In addition, the adhesive portion 220 may have an adhesive force of 1 N/25 mm or more to the substrate 210 . In addition, the adhesive part 220 may have adhesive strength on both surfaces.

In addition, the dielectric constant of the adhesive part 220 is 3.5 or less at a frequency of 100 kHz to 2 MHz region, and the moisture permeability may be 500 g/m2 E24hr or more, but this is only an exemplary value and the present invention is not limited thereto.

The adhesive part 220 may be formed of a polyurethane resin, an acrylic resin, a natural rubber resin, a synthetic rubber resin, a silicone resin, or a combination thereof.

The flexible electrode part 230 may be formed on one surface of the substrate 210 , that is, on a surface opposite to the surface to which the adhesive is attached. The flexible electrode unit 230 may include a plurality of electrodes as illustrated in FIG. 2 . The flexible electrode unit 230 may be formed by printing on the substrate 210 .

The flexible electrode part 230 of the glucose sensor according to an embodiment of the present invention may be made of a conductive polymer. For example, the conductive polymer may be one or more polymerized from the group consisting of thionine, aniline, pyrrole, and thiophene. More specifically, the conductive polymer is polythiophene, polypyrrole, polyaniline, polyfluorene, polyacetylene, poly(p-phenylene vinylene), poly(3,4-ethylenedioxythiophene), poly(3,4- propylenedioxythiophene) and poly(3,3-dibenzyl3,4-propylenedioxythiophene), poly(3-4-ethylenedioxythiophene), bis-poly(ethylene glycol), lauryl terminated, poly( 3,4-ethylenedioxythiophene)-block PEG, poly(3,4-ethylenedioxythiophene), tetramethacrylate endcaps, or combinations thereof.

In addition, in one embodiment, the flexible electrode unit 230 may be a mixture of a conductive polymer and an electron transport medium. For example, electron transport mediators include hexaamineruthenium (III) chloride (hexaammineruthenium (III) chloride), potassium ferricyanide, potassium ferrocyanide, dimethyl ferrocene (DMF), Ferricinium, ferrocene monocarboxylic acid (FCOOH), 7,7,8,8,-tetracyanoquinodimethane (7,7,8,8-tetracyanoquino-dimethane (TCNQ) )), tetrathia fulvalene (TTF), nickel locene (Nc), N-methyl acidinium (NMA+), tetrathiatetracene (TTT) ), N-methylphenazinium (NMP+), hydroquinone, 3-dimethylaminobenzoic acid (MBTHDMAB), 3-methyl-2-benzothiozorinonehydra Zone (3-methyl2-benzothiozolinone hydrazone), 2-methoxy-4-allylphenol (2-methoxy-4-allylphenol), 4-aminoantipyrin (AAP), dimethylaniline (dimethylaniline), 4- Aminoantipyrene, 4-methoxynaphthol, 3,3',5,5'-tetramethylbenzidine (3,3',5,5'-tetramethyl benzidine (TMB)) , 2,2-azino-di-[3-ethyl-benzthiazoline sulfonate] (2,2-azino-di-[3-ethyl-benzthiazoline sulfonate]), o-dianisidine, o- Toluidine (o-toluidine), 2,4-dichlorophenol (2,4-dichlorophenol), 4-aminophenazone (4-amino ph enazone), benzidine, Prussian blue, bipyridine-osmium complex compound, etc. may be used.

In this case, the hydrogen peroxide decomposition material in the total solid content of the conductive polymer and the electron transport medium mixture constituting the flexible electrode part 230 may be 0.1 to 20 wt%.

A glucose reaction unit 240 may be formed on the flexible electrode unit 230 . In addition, the electrolyte supply layer 250 may be formed on the glucose reaction unit 240 .

On the other hand, the tensile force of the glucose sensor 200 according to an embodiment of the present invention may be 5N or less when 10% tension.

4 shows a result of comparing elongation rates between a glucose sensor and another glucose sensor according to an embodiment of the present invention.

In FIG. 4, A is a conventional glucose sensor, and B to D are cases in which the flexible electrode part is made of a conductive polymer according to an embodiment of the present invention.

As shown in FIG. 4 , in case of A, cracks occurred at an elongation of 10% or less, but in cases of B to D, cracks did not occur even at elongations of 20, 30, and 40%, respectively.

As a result, due to the characteristics of the wearable glucose sensor attached to the skin, stretching of various sizes is required for the glucose sensor. The wearable glucose sensor according to an embodiment of the present invention cracks even at a larger stretching than the conventional wearable glucose sensor. It has the advantage of being able to maintain its original shape without doing so.

In addition, there is an advantage that the overall process can be reduced by simplifying the double structure into a single structure by forming the electrode itself with a conductive polymer, unlike the conventional forming of an electrode on a substrate and forming an electron transporting part on the electrode.

210: substrate
220: adhesive
230: flexible electrode part
240: glucose reaction unit
250: electrolyte supply layer
70: wiring part
100: temperature sensor

Claims (10)

a substrate on which an adhesive is formed on one surface;
a flexible electrode part formed on another surface of the substrate; and
and a glucose reaction unit formed on the flexible electrode unit,
The flexible electrode part includes a conductive polymer.
biosensor. According to claim 1,
The conductive polymer is one or more selected from the group consisting of thionine, aniline, pyrrole and thiophene is polymerized
biosensor. According to claim 1,
The flexible electrode part is composed of a mixture of a conductive polymer and an electron transport medium.
biosensor. 4. The method of claim 3,
Among the total solids of the mixture of the conductive polymer and the electron transport media, the electron transport mediator is 0.1 to 20 wt%.
biosensor. According to claim 1,
The elastic modulus of the adhesive is 0.01 to 100 Mpa at 25 ℃
biosensor According to claim 1,
Adhesion of the pressure-sensitive adhesive to the substrate is 1 N/25mm or more
biosensor. According to claim 1,
The dielectric constant of the pressure-sensitive adhesive is 3.5 or less at a frequency of 100 kHz to 2 MHz.
biosensor. According to claim 1,
The moisture permeability of the adhesive is 500 g/m2 E24hr or more
biosensor. According to claim 1,
The tensile force of the wearable glucose sensor is 5 N or less at 10% tensile strength.
biosensor. According to claim 1,
Further comprising an electrolyte supply layer on the glucose reaction unit
biosensor.

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