WO2018004191A1 - Dispositif de biodétection et dispositif d'administration de médicament - Google Patents

Dispositif de biodétection et dispositif d'administration de médicament Download PDF

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Publication number
WO2018004191A1
WO2018004191A1 PCT/KR2017/006572 KR2017006572W WO2018004191A1 WO 2018004191 A1 WO2018004191 A1 WO 2018004191A1 KR 2017006572 W KR2017006572 W KR 2017006572W WO 2018004191 A1 WO2018004191 A1 WO 2018004191A1
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WO
WIPO (PCT)
Prior art keywords
electrode
sensor
phase change
layer
glucose
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Application number
PCT/KR2017/006572
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English (en)
Korean (ko)
Inventor
김대형
현택환
최승홍
송창영
이현재
Original Assignee
서울대학교 산학협력단
기초과학연구원
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Priority claimed from KR1020160081447A external-priority patent/KR101933760B1/ko
Priority claimed from KR1020160081453A external-priority patent/KR101789716B1/ko
Priority claimed from KR1020160081450A external-priority patent/KR101843263B1/ko
Application filed by 서울대학교 산학협력단, 기초과학연구원 filed Critical 서울대학교 산학협력단
Publication of WO2018004191A1 publication Critical patent/WO2018004191A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
    • G01N27/04—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance
    • G01N27/14—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of an electrically-heated body in dependence upon change of temperature
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material

Definitions

  • the present invention relates to a biosensing device and a drug delivery device.
  • the present invention provides a highly reliable bio-sensing device.
  • the present invention provides a highly integrated bio sensing device.
  • the present invention provides a wearable bio-sensing device having elasticity.
  • the present invention provides a biosensing device capable of accurately measuring the concentration of glucose in the human body in a non-invasive manner.
  • the present invention provides a biosensing device that can be used for a single use.
  • the present invention provides a drug delivery device that can inject drugs into the human body.
  • the present invention provides a drug delivery device that can adjust the amount of drug to be injected into the human body.
  • the present invention provides a drug delivery device that can inject glucose control drugs into the human body.
  • the biosensing device includes a support layer and a biosensor disposed on the support layer.
  • the biosensor may include a glucose sensor.
  • the glucose sensor may include a first electrode and a second electrode disposed adjacent to the first electrode, and the second electrode may surround the first electrode.
  • the glucose sensor may further include a third electrode disposed adjacent to the first electrode, and the second electrode and the third electrode may surround the first electrode.
  • the first electrode may include a porous gold layer, a hydrogen peroxide decomposition layer disposed on the porous gold layer, and a glucose decomposition layer disposed on the hydrogen peroxide decomposition layer.
  • the diameter of the first electrode may be 800 ⁇ 1,000 ⁇ m, the diameter of the glucose sensor may be 2 ⁇ 3mm.
  • the first electrode may have a circular shape or a polygonal shape
  • the outline of the glucose sensor may have a circular shape or a polygonal shape.
  • the biosensor may further include a humidity sensor disposed adjacent to the glucose sensor.
  • the humidity sensor may include a comb-shaped first electrode and a comb-shaped second electrode disposed adjacent to the first electrode, and the comb teeth of the first electrode and the comb teeth of the second electrode are alternately disposed. Can be arranged.
  • the biosensor may further include a pH sensor disposed adjacent to the glucose sensor.
  • the pH sensor may include a second electrode and a first electrode disposed adjacent to the second electrode, and the first electrode may surround the second electrode.
  • the pH sensor may include a second electrode and two first electrodes disposed adjacent to the second electrode, and the two first electrodes may surround the second electrode.
  • the biosensor is disposed adjacent to the glucose sensor, and may further include one or two or more of a humidity sensor, a pH sensor, and a temperature sensor.
  • the glucose sensor may measure the glucose concentration in the sweat
  • the humidity sensor may measure the amount of sweat required to measure the glucose concentration
  • the pH sensor may measure the pH of the sweat
  • the temperature The sensor can measure the temperature of the sweat.
  • the glucose concentration measured by the glucose sensor may be corrected by one or two of the pH of the sweat measured by the pH sensor and the temperature of the sweat measured by the temperature sensor.
  • the bio-sensing device may further include a wiring pattern formed on the support layer.
  • the wiring pattern may include a first wiring pattern connected to the humidity sensor, a second wiring pattern connected to the glucose sensor, a third wiring pattern connected to the pH sensor, and a fourth wiring pattern connected to the temperature sensor. It may include.
  • the wiring pattern may have a serpentine shape.
  • the bio-sensing device may further include a first insulating layer disposed between the wiring pattern and the support layer and a second insulating layer disposed on the wiring pattern.
  • the second insulation layer may expose the humidity sensor, the glucose sensor, and the pH sensor, and the first insulation layer and the second insulation layer may have a serpentine shape.
  • the bio-sensing device may further include a screen layer disposed on the glucose sensor.
  • the glucose sensor may measure glucose concentration in the sweat, and the screen layer may remove foreign substances from the sweat provided to the glucose sensor.
  • the biosensing device may further include a sweat absorbing layer disposed on the biosensor.
  • the bio-sensing device may further include a waterproof layer disposed under the support layer.
  • the support layer may be a silicon patch.
  • the biosensor may include a first electrode and a second electrode disposed adjacent to the first electrode, and the second electrode may surround the first electrode.
  • the biosensor may further include a third electrode disposed adjacent to the first electrode, and the second electrode and the third electrode may surround the first electrode.
  • the biosensor may include a comb-shaped first electrode and a comb-shaped second electrode disposed adjacent to the first electrode, and the comb teeth of the first electrode and the comb teeth of the second electrode alternate with each other. Can be arranged.
  • the biosensor may include a first electrode and two second electrodes disposed adjacent to the first electrode, and the two second electrodes may surround the first electrode.
  • a biosensing device includes a support layer, a spacer disposed on both sides of the support layer, a biosensor disposed on the support layer between the spacers, and a cover layer disposed on the spacer to be spaced apart from the biosensor. It includes.
  • the biosensor may include a glucose sensor.
  • the glucose sensor may include a first electrode and a second electrode disposed adjacent to the first electrode, and the second electrode may surround the first electrode.
  • the glucose sensor may further include a third electrode disposed adjacent to the first electrode, and the second electrode and the third electrode may surround the first electrode.
  • the first electrode may include a porous gold layer, a hydrogen peroxide decomposition layer disposed on the porous gold layer, and a glucose decomposition layer disposed on the hydrogen peroxide decomposition layer.
  • the diameter of the first electrode may be 800 ⁇ 1,000 ⁇ m, the diameter of the glucose sensor may be 2 ⁇ 3mm.
  • the first electrode may have a circular shape or a polygonal shape
  • the outline of the glucose sensor may have a circular shape or a polygonal shape.
  • the biosensor may further include a pH sensor disposed adjacent to the glucose sensor.
  • the pH sensor may include a second electrode and a first electrode disposed adjacent to the second electrode, and the first electrode may surround the second electrode.
  • the pH sensor may include a second electrode and two first electrodes disposed intimately with the second electrode, and the two first electrodes may surround the second electrode.
  • the biosensor may be disposed adjacent to the glucose sensor and further include one or two of a pH sensor and a temperature sensor.
  • the glucose sensor may measure the glucose concentration in the sweat
  • the pH sensor may measure the pH of the sweat
  • the temperature sensor may measure the temperature of the sweat.
  • the glucose concentration measured by the glucose sensor may be corrected by one or two of the pH of the sweat measured by the pH sensor and the temperature of the sweat measured by the temperature sensor.
  • the bio-sensing device may further include a wiring pattern formed on the support layer.
  • the wiring pattern may include a first wiring pattern connected to the glucose sensor, a second wiring pattern connected to the pH sensor, and a third wiring pattern connected to the temperature sensor.
  • the biosensing device may further include an insulating layer disposed on the wiring pattern, and the insulating layer may expose the glucose sensor and the pH sensor.
  • the insulating layer may be disposed between the support layer and the spacer.
  • the bio-sensing device may further include a screen layer disposed on the glucose sensor.
  • the glucose sensor may measure glucose concentration in the sweat, and the screen layer may remove foreign substances from the sweat provided to the glucose sensor.
  • the cover layer may be formed of a sweat absorbing layer.
  • the support layer, the spacer, and the cover layer may define a sweat absorption gap capable of absorbing sweat on the front of the bio-sensing device.
  • the bio-sensing device may further include a waterproof layer disposed under the support layer.
  • the support layer may be a polymer strip.
  • the biosensor may include a first electrode and a second electrode disposed adjacent to the first electrode, and the second electrode may surround the first electrode.
  • the biosensor may further include a third electrode disposed adjacent to the first electrode, and the second electrode and the third electrode may surround the first electrode.
  • the biosensor may include a first electrode and two second electrodes disposed adjacent to the first electrode, and the two second electrodes may surround the first electrode.
  • the drug delivery device includes a drug delivery unit including microneedles and phase change nanoparticles disposed in the microneedles and loaded with drugs.
  • the phase change nanoparticle may include a phase change material loaded with the drug and a ligand compound surrounding the phase change material.
  • the phase change nanoparticle may include a first phase change nanoparticle and a second phase change nanoparticle, and the first phase change nanoparticle may include a first phase change material having a first phase change temperature.
  • the second phase change nanoparticle may include a second phase change material having a second phase change temperature. The second phase change temperature may be higher than the first phase change temperature.
  • the first phase change temperature may be lower than 40 ° C.
  • the second phase change temperature may be higher than 40 ° C.
  • the first phase change material may be formed of palm oil, and the second phase change material may be formed of tridecanoic acid.
  • the ligand compound may be a substance capable of forming an O / W emulsion.
  • the ligand compound may include DOPA-HA (3,4-Dihydroxyl-L-phenylalanine (DOPA) -conjugated hyaluronic acid).
  • the drug delivery unit may further include a phase change layer coated on the surface of the microneedle, and the phase change layer may be formed of tetradecanol.
  • the drug delivery unit may further include a microneedle bonding layer coupled to the microneedle to support the microneedle, and the microneedle and the microneedle bonding layer may be integrally formed.
  • the microneedle and the microneedle bonding layer may be formed of a hyaluronic acid hydrogel.
  • the drug may include a glucose regulating drug.
  • the drug delivery device may further include a heating unit coupled to the drug delivery unit and heating the drug delivery unit.
  • the drug loaded on the phase change nanoparticles may be released by the heating unit heating the drug delivery unit.
  • the heating unit may include one or more heaters.
  • the heater may include a first heater and a second heater.
  • the drug loaded on the phase change nanoparticles may be sequentially released step by step.
  • the phase change nanoparticle may include a phase change material loaded with the drug, and the phase change nanoparticle may include a first phase change nanoparticle and a second phase change nanoparticle, and the first phase change
  • the nanoparticles may include a first phase change material having a first phase change temperature
  • the second phase change nanoparticles may include a second phase change material having a second phase change temperature.
  • the second phase change temperature may be higher than the first phase change temperature.
  • the drug When the drug delivery unit is heated to a temperature higher than the second phase change temperature by the first heater, the drug may be released to the second phase change nanoparticle disposed on the first heater. The loaded drug may be released.
  • the drug delivery unit When the drug delivery unit is heated to a temperature between the first phase change temperature and the second phase change temperature by the second heater, the drug delivery unit is loaded on the first phase change nanoparticles disposed on the second heater. Drug can be released, and when the drug delivery unit is heated to a temperature higher than the second phase change temperature by the second heater, to the second phase change nanoparticles of the drug delivery unit disposed on the second heater The loaded drug may be released.
  • the heating unit may further include a temperature sensor disposed to be spaced apart from the heater.
  • the heating unit may include a support layer, a heater disposed on the support layer, and a temperature sensor disposed to be spaced apart from the heater on the support layer.
  • the heating unit may further include a waterproof layer disposed under the support layer.
  • the biosensing device according to embodiments of the present invention may have excellent reliability.
  • the bio-sensing device can accurately diagnose disease or measure biological signals.
  • the biosensing device may be highly integrated.
  • the biosensor included in the biosensor may be miniaturized so that a plurality of various sensors may be integrated in a small area.
  • the biosensing device may have elasticity and be attached to a human body.
  • the bio-sensing device may have elasticity that can maintain reliability even when deformed by a user's operation.
  • the bio-sensing device is attached to the human body to perform diagnosis and measurement on the human body in real time, and is effective and convenient to use, so anyone can use it easily.
  • Biosensing device can accurately measure the glucose concentration of the human body in a non-invasive manner.
  • the bio-sensing device can measure glucose concentration in sweat.
  • a biosensor such as a glucose sensor included in the biosensing device, can be miniaturized so that the glucose concentration can be accurately measured even with a small amount of sweat.
  • the glucose sensor may include a porous gold layer having a large electrochemically active surface so that glucose concentration can be accurately measured even with a small amount of sweat.
  • the bio-sensing device may check whether sweat collected for glucose sensing is collected by a humidity sensor.
  • the biosensing device can measure the glucose concentration more accurately by measuring the glucose concentration measured by the glucose sensor by the pH sensor and / or the temperature sensor.
  • the bio-sensing device can easily and efficiently collect the sweat necessary for sensing by the sweat-absorbing layer.
  • the bio-sensing device may remove foreign substances from sweat used for glucose sensing by the screen layer.
  • the bio-sensing device can prevent the sweat used for glucose sensing from being discharged to the outside by the waterproof layer, and prevent foreign substances such as external moisture that prevents glucose sensing from penetrating into the bio-sensing device.
  • the biosensing device according to the embodiments of the present invention may be used for a single use.
  • the bio-sensing device can be miniaturized into a strip shape and can easily collect sweat through a sweat absorption gap, and thus can be conveniently used for a single use.
  • the bio-sensing device can collect sweat more easily by forming a cover layer as a sweat absorbing layer.
  • the bio-sensing device may be used by attaching to the human body by including a waterproof layer, and may be effectively attached to a user who has little sweat or does not sweat well.
  • Drug delivery device can inject drugs into the human body.
  • the drug delivery device may adjust the amount of drug injected into the human body.
  • the drug delivery device may sequentially inject drugs step by step according to the user's condition.
  • the drug delivery device may inject glucose control drugs into the human body.
  • the drug delivery device may adjust the amount of glucose regulating drug injected into the human body according to the glucose concentration in the human body of the user.
  • the drug delivery device may sequentially release the glucose regulating drug step by step, thereby allowing the user to effectively regulate glucose in the human body.
  • the drug delivery device may be repeatedly used to release the glucose control drug several times after being attached to the human body, and thus may be used for a long time.
  • FIG. 1 is a plan view of a bio-sensing device according to an embodiment of the present invention.
  • FIG. 2 is an exploded perspective view of the biosensing device of FIG. 1.
  • FIG. 3 shows an actual image of the biosensing device of FIG. 1.
  • FIG. 4 is a plan view of a humidity sensor according to an embodiment of the present invention.
  • FIG. 5 shows a calibration curve of the humidity sensor of FIG.
  • FIG. 6 is a plan view of a humidity sensor according to another embodiment of the present invention.
  • FIG. 7 is a plan view of a glucose sensor according to an embodiment of the present invention.
  • FIG. 8 is an exploded perspective view of the glucose sensor of FIG. 7.
  • FIG. 9 illustrates a calibration curve of the glucose sensor of FIG. 7.
  • FIG 11 shows an SEM image of the porous gold layer and the glucose decomposition layer of the glucose sensor.
  • FIG. 12 shows hydrogen peroxide sensing performance of the porous gold layer and the planar gold layer.
  • FIG. 13 shows the CV curves of the porous gold layer and the planar gold layer.
  • 16 to 18 are plan views of glucose sensors according to still other embodiments of the present invention.
  • 19 is a plan view of a pH sensor according to an embodiment of the present invention.
  • 21 is a plan view of a pH sensor according to another embodiment of the present invention.
  • 22 to 24 are plan views of pH sensors according to yet another exemplary embodiment of the present invention.
  • 25 is a plan view of a temperature sensor according to an embodiment of the present invention.
  • FIG. 26 illustrates a calibration curve of the temperature sensor of FIG. 25.
  • 29 to 38 illustrate a method of forming a biosensor according to an embodiment of the present invention.
  • 39 is a plan view of a biosensor according to another embodiment of the present invention.
  • FIG. 40 is an exploded perspective view of the biosensing device of FIG. 39.
  • FIG. 41 is a front view of the biosensing device of FIG. 39.
  • FIG. 42 illustrates an actual image of the biosensing device of FIG. 39.
  • FIG. 43 is a diagram for describing a method of using the biosensing device of FIG. 39.
  • 44 to 47 illustrate a method of forming a biosensor according to another embodiment of the present invention.
  • FIG. 48 is a perspective view of a drug delivery device according to one embodiment of the present invention.
  • FIG. 49 is an exploded perspective view of the drug delivery device of FIG. 48.
  • FIG. 50 shows an actual image of the drug delivery device of FIG. 48.
  • 51 is an enlarged partial view of a drug delivery unit according to an embodiment of the present invention.
  • 53 to 55 illustrate a method of forming a drug delivery unit according to an embodiment of the present invention.
  • FIG. 56 illustrates a wearable bio system according to an embodiment of the present invention.
  • first and second are used herein to describe various elements, the elements should not be limited by such terms. These terms are only used to distinguish the elements from one another. Again, where an element is said to be above another element it means that it can be formed directly on another element or a third element can be interposed therebetween.
  • 'A' having a circular shape means that 'A' may have an elliptical shape as well as a circular shape.
  • 'A' surrounding 'B' means that 'A' may have a shape that extends to face the center of 'B' even though 'A' does not completely surround 'B'.
  • the bio-sensing device and the drug delivery device measure glucose concentration in sweat, and use the same to control the glucose in the human body as an example, but the present disclosure is not limited thereto.
  • various secretions of the human body for example, the concentration of glucose in the urine can be measured and used to control glucose in the human body of the user.
  • the subject of measurement and regulation can be extended to other than glucose.
  • FIG. 1 is a plan view of a bio sensing device according to an embodiment of the present invention
  • FIG. 2 is an exploded perspective view of the bio sensing device of FIG. 1
  • FIG. 3 shows an actual image of the bio sensing device of FIG. 1.
  • the biosensor 10 may include a biosensor 100, a wiring pattern 150, a support layer 160, a first insulating layer 161, a second insulating layer 162, and a screen.
  • the layer 170, the sweat absorbing layer 180, and the waterproof layer 190 may be included.
  • the biosensor 100 may include a humidity sensor 110, a glucose sensor 120, a pH sensor 130, and a temperature sensor 140.
  • the wiring pattern 150 may include a first wiring pattern 151, The second wiring pattern 152, the third wiring pattern 153, and the fourth wiring pattern 154 may be included.
  • the wiring pattern 150 may be formed of a conductive material, for example, a metal such as gold (Au), platinum (Pt), aluminum (Al), nickel (Ni), or a metal oxide such as ITO.
  • the wiring pattern 150 may be formed of a double layer such as a chromium layer / gold layer (Cr / Au).
  • the humidity sensor 110 may include a first electrode 111 and a second electrode 112.
  • the first electrode 111 and the second electrode 112 of the humidity sensor 110 may be disposed on the first wiring pattern 151 electrically separated from each other.
  • the humidity sensor 110 may be electrically connected to the external device by the first wiring pattern 151.
  • the first wiring pattern 151 may have a serpentine shape.
  • the humidity sensor 110 may measure an amount of sweat (humidity) by measuring an impedance between the first electrode 111 and the second electrode 112.
  • the humidity sensor 110 sets a threshold amount of sweat (critical humidity) that reliably measures the glucose concentration measurement by the glucose sensor 120 and monitors the amount of sweat. If the humidity value measured by the humidity sensor 110 is equal to or greater than the threshold humidity value, the glucose sensor 120, the pH sensor 130, and the temperature sensor 140 start measuring.
  • the glucose sensor 120 may include a first electrode 121, a second electrode 122, and a third electrode 123.
  • the first electrode 121 may be a woking electrode
  • the second electrode 122 may be a counter electrode
  • the third electrode 123 may be a reference electrode.
  • the glucose sensor 120 is a three-electrode sensor, but is not limited thereto, and may be formed as a two-electrode sensor.
  • the first electrode 121, the second electrode 122, and the third electrode 123 of the glucose sensor 120 may be disposed on the second wiring pattern 152 electrically separated from each other.
  • the glucose sensor 120 may be electrically connected to the external device by the second wiring pattern 152.
  • the second wiring pattern 152 may have a serpentine shape.
  • the glucose sensor 120 measures the glucose concentration in the sweat when the humidity value measured by the humidity sensor 110 is greater than or equal to the threshold humidity value.
  • the glucose sensor 120 has a structure in which the second electrode 122 and the third electrode 123 surround the first electrode 121 so that not only the glucose sensor 120 but also the entire biosensor 10 may be highly integrated. Can be.
  • the first electrode 121 may be formed in a small size having a diameter of about 1,000 ⁇ m or less, thereby accurately measuring the glucose concentration in sweat even with a small amount of sweat of about 1 ⁇ l.
  • One or more glucose sensors 120 may be disposed. By placing two or more glucose sensors 120 in place, sweat glucose concentration can be measured more accurately.
  • the pH sensor 130 may include a first electrode 131 and a second electrode 132.
  • the first electrode 131 may be a working electrode
  • the second electrode 132 may be a reference electrode and / or a counter electrode.
  • the first electrode 131 may be a reference electrode and / or a counter electrode
  • the second electrode 132 may be a working electrode.
  • the pH sensor 130 is a two-electrode sensor, but is not limited thereto, and may be formed of a three-electrode sensor such as the glucose sensor 120.
  • the first electrode 131 and the second electrode 132 of the pH sensor 130 may be disposed on the third wiring pattern 153 that is electrically separated from each other.
  • the pH sensor 130 may be electrically connected to the external device by the third wiring pattern 153.
  • the third wiring pattern 153 may have a serpentine shape.
  • the pH sensor 130 measures the pH of the sweat when the humidity value measured by the humidity sensor 110 is greater than or equal to the threshold humidity value.
  • the pH sensor 130 may measure the pH of the sweat by measuring a change in the open circuit potential (OCP) between the first electrode 131 and the second electrode 132.
  • OCP open circuit potential
  • the glucose concentration measurement value may be corrected in real time according to the pH value measured by the pH sensor 130.
  • the pH sensor 130 may be disposed one or more than one. By placing two or more pH sensors 130 in place, the pH of the sweat can be measured more accurately.
  • the pH sensor 130 may function as two pH sensors by disposing two first electrodes 131 around the second electrode 132. Two first electrodes 131 may surround the second electrode 132. Accordingly, two second electrodes 132 disposed apart from each other with the glucose sensor 120 interposed therebetween, and two pairs of first electrodes 131 disposed around the second electrode 132 substantially have four pH sensors. Can function as
  • the temperature sensor 140 is disposed on the first insulating layer 161 and connected to the fourth wiring patterns 154 separated from each other.
  • the temperature sensor 140 and the fourth wiring pattern 154 may have a serpentine shape.
  • the temperature sensor 140 measures the temperature of the sweat when the humidity value measured by the humidity sensor 110 is equal to or greater than the threshold humidity value.
  • the temperature sensor 140 may measure a temperature of sweat by measuring an electrical resistance value according to a temperature change as a resistor.
  • the glucose concentration measurement value may be corrected in real time according to the temperature value measured by the temperature sensor 140.
  • the biosensor 100 includes, but is not limited to, a humidity sensor 110, a pH sensor 130, and a temperature sensor 140 to more accurately measure glucose concentration.
  • the sensors may not be included or one or more may be selected and included.
  • the support layer 160 is disposed under the biosensor 100 and the wiring pattern 150 to support the biosensor 100 and the wiring pattern 150.
  • the support layer 160 may be formed of a silicone polymer, for example, polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • the support layer 160 may be a silicon patch.
  • the first insulating layer 161 is disposed between the wiring pattern 150 and the support layer 160, and the second insulating layer 162 is disposed on the wiring pattern 150.
  • the first insulating layer 161 and / or the second insulating layer 162 may have a serpentine shape and may have elasticity.
  • the first insulating layer 161 and the second insulating layer 162 may be formed of, for example, polyimide, epoxy, or the like.
  • the second insulating layer 162 exposes an end region of the biosensor 100 and the wiring pattern 150, whereby the biosensor 100 may be in contact with sweat, and the end region of the wiring pattern 150. May be electrically connected to an external device. However, the second insulating layer 162 may be covered without exposing the temperature sensor 140.
  • the screen layer 170 is disposed above the glucose sensor 120.
  • the screen layer 170 may filter out foreign substances (including drugs) that may interfere with sensing glucose in the sweat absorbed through the sweat absorbing layer 180.
  • the screen layer 170 may stably fix the glucose decomposition layer (121c of FIG. 8) of the first electrode 121 of the glucose sensor 120.
  • the screen layer 170 may be formed of, for example, Nafion®.
  • the sweat absorbing layer 180 is disposed on the biosensor 100.
  • the sweat absorbing layer 180 absorbs sweat and provides the sweat to the biosensor 100. Even if the amount of sweat emitted from the human body is small, the sweat may be absorbed by the sweat absorbing layer 180 and collected quickly and easily.
  • Sweat absorbing layer 180 may be formed of a porous material, for example, a fibrous material such as cotton can absorb and discharge sweat well.
  • the waterproof layer 190 is disposed below the support layer 160.
  • the waterproof layer 190 may prevent moisture other than sweat from penetrating into the biosensor 100 after the biosensing device 10 is attached to the human body, and sweat is absorbed by the sweat absorbing layer 180 in the support layer 160 region. Can help to be collected.
  • the waterproof layer 190 allows the support layer 160 to be more stably attached to the human body.
  • the waterproof layer 190 may be formed of, for example, Tegagerm®.
  • FIG. 4 is a plan view of a humidity sensor according to an embodiment of the present invention.
  • the humidity sensor 110 may include a first electrode 111 and a second electrode 112.
  • the first electrode 111 and the second electrode 112 may have a comb shape. Comb teeth of the first electrode 111 is inserted into the groove of the second electrode 112, comb teeth of the second electrode 112 is inserted into the groove of the first electrode 112, comb teeth of the first electrode 111. Combs of the second electrode 112 and the comb teeth may be alternately arranged.
  • the outline of the humidity sensor 110 has a circular shape, but is not limited thereto and may have a polygonal shape. Referring to FIG. 6, the outline of the humidity sensor 110 may have a rectangular shape.
  • the humidity sensor 110 may have a diameter of about 2 to 3 mm.
  • the first electrode 111 and the second electrode 112 may be formed of a conductive material such as poly (3,4-ethylenedioxythiophene) (PEDOT).
  • PEDOT poly (3,4-ethylenedioxythiophene)
  • FIG. 5 shows a calibration curve of the humidity sensor of FIG.
  • the impedance between the first electrode 111 and the second electrode 112 when the impedance between the first electrode 111 and the second electrode 112 is about 10 7 ⁇ or the amount of sweat is about 1 ⁇ l or more, the impedance may be about 10 3 ⁇ or less. Decreases. As such, the humidity sensor 110 may measure humidity by measuring an impedance between the first electrode 111 and the second electrode 112.
  • FIG. 7 is a plan view of a glucose sensor according to an embodiment of the present invention
  • FIG. 8 is an exploded perspective view of the glucose sensor of FIG. 7.
  • the glucose sensor 120 may include a first electrode 121, a second electrode 122, and a third electrode 123.
  • the outline of the first electrode 121 and the glucose sensor 120 has a circular shape, but is not limited thereto. 14 and 15, an outline of the first electrode 121 and the glucose sensor 120 may have a polygonal shape such as a rectangle or a triangle.
  • the diameter of the first electrode 121 may be about 800 to 1,000 ⁇ m, and the diameter of the glucose sensor 120 may be about 2 to 3 mm.
  • the first electrode 121 may include a porous gold layer 121a, a hydrogen peroxide decomposition layer 121b disposed on the porous gold layer 121a, and a glucose decomposition layer 121c disposed on the hydrogen peroxide decomposition layer 121c.
  • the glucose decomposition layer 121c may include glucose oxidase, a glucose decomposition enzyme, and may form hydrogen peroxide by decomposing glucose in sweat.
  • the hydrogen peroxide decomposition layer 121b may include Prussian blue, which serves as a catalyst for hydrogen peroxide decomposition, and may decompose hydrogen peroxide formed by decomposition of glucose in the glucose decomposition layer 121c.
  • the porous gold layer 121a may trap electrons generated by decomposition of hydrogen peroxide. That is, when glucose is present in the sweat, the glucose decomposition layer 121c decomposes the glucose to generate hydrogen peroxide, and the hydrogen peroxide decomposition layer 121b decomposes the hydrogen peroxide to generate electrons, and the porous gold layer 121a is generated. Electrons are captured to generate an electrical signal. Glucose concentration may be measured by the electrical signal.
  • the porous gold layer 121a may maximize the electrochemically active surface, thereby accurately measuring the concentration of hydrogen peroxide decomposed by the hydrogen peroxide decomposition layer 121b. This makes it possible to accurately measure sweat glucose concentration even with a small amount of sweat of about 1 ⁇ l.
  • the porous gold layer 121a can stably fix the glucose decomposition layer by the porous structure.
  • the second electrode 122 may be formed of a conductive material such as chromium layer / platinum layer (Cr / Pt), and the third electrode 123 may be formed of a conductive material such as silver layer / silver chloride layer (Ag / AgCl). Can be.
  • a conductive material such as chromium layer / platinum layer (Cr / Pt)
  • the third electrode 123 may be formed of a conductive material such as silver layer / silver chloride layer (Ag / AgCl). Can be.
  • FIG. 9 illustrates a calibration curve of the glucose sensor of FIG. 7.
  • the glucose concentration in the sweat is increased in the range of 10 ⁇ M to 1 mM, which is a typical glucose concentration in the human sweat, the measured value of the glucose sensor increases proportionally. This indicates that the glucose concentration in the sweat can be accurately measured by the glucose sensor.
  • the amount of sweat required to measure glucose concentration may be reduced to a small amount of about 1 ⁇ l.
  • FIG 11 shows an SEM image of the porous gold layer and the glucose decomposition layer of the glucose sensor.
  • the image on the left shows the porous gold layer and the image on the right shows the glucose degradation layer (glucose oxidase).
  • the porous gold layer is formed by electrodepostion, and the glucose decomposition layer is formed by crosslinking on the porous gold layer by drop casting.
  • the glucose decomposition layer can be stably fixed on the porous gold layer.
  • FIG. 12 shows hydrogen peroxide sensing performance of the porous gold layer and the planar gold layer.
  • the porous gold layer on which the hydrogen peroxide decomposition layer increases as the hydrogen peroxide concentration increases in proportion to the hydrogen peroxide concentration, but the planar gold layer on which the hydrogen peroxide decomposition layer is deposited. Au) does not change proportionately with increasing hydrogen peroxide. Since the porous gold layer has a larger electrochemically active surface than the planar gold layer, the hydrogen peroxide concentration is excellent.
  • FIG. 13 shows the CV curves of the porous gold layer and the planar gold layer.
  • the porous gold layer has a higher charge storage capacitance than the planar gold layer.
  • the porous gold layer has a lower interface impedance than the planar gold layer.
  • 16 to 18 are plan views of glucose sensors according to still other embodiments of the present invention.
  • the glucose sensor 120 may include a first electrode 121 and a second electrode 122.
  • the first electrode 121 may be a working electrode
  • the second electrode 122 may be a reference electrode and / or a counter electrode. That is, the glucose sensor 120 may be a two-electrode sensor.
  • the second electrode 122 may surround the first electrode 121.
  • the outline of the first electrode 121 and the glucose sensor 120 may have a circular shape or a polygonal shape such as a rectangle or a triangle.
  • 19 is a plan view of a pH sensor according to an embodiment of the present invention.
  • the pH sensor 130 may include a first electrode 131 and a second electrode 132.
  • Two first electrodes 131 may be disposed around the second electrode 132 such that the pH sensor 130 may function as two pH sensors.
  • the outline of the second electrode 132 and the pH sensor 130 has a circular shape, but is not limited thereto.
  • an outline of the second electrode 132 and the pH sensor 130 may have a polygonal shape such as a quadrangle.
  • the diameter of the second electrode 132 may be about 800 to 1,000 ⁇ m, and the diameter of the pH sensor 130 may be about 2 to 3 mm.
  • the first electrode 131 may be formed of a conductive material such as polyaniline
  • the second electrode 132 may be formed of a conductive material such as silver layer / silver chloride layer (Ag / AgCl).
  • the pH value measured by the pH sensor when the open circuit potential (OCP) between the first electrode 131 and the second electrode 132 increases from ⁇ 80 mV to 160 mV with time is 7 Decreases to 4 In this way, the pH of the sweat can be measured by measuring the OCP between the first electrode 131 and the second electrode 132.
  • 22 to 24 are plan views of pH sensors according to yet another exemplary embodiment of the present invention.
  • the pH sensor 130 may include a first electrode 131 and a second electrode 132.
  • the first electrode 131 may be a working electrode
  • the second electrode 132 may be a reference electrode and / or a counter electrode.
  • the first electrode 131 may be a reference electrode and / or a counter electrode
  • the second electrode 132 may be a working electrode.
  • the first electrode 131 may surround the second electrode 132.
  • the outline of the second electrode 132 and the pH sensor 132 may have a circular shape or a polygonal shape such as a square or a triangle.
  • 25 is a plan view of a temperature sensor according to an embodiment of the present invention.
  • the temperature sensor 140 may measure a temperature of sweat by measuring an electrical resistance value according to a temperature change as a resistor.
  • the temperature sensor 140 may have a serpentine shape.
  • the temperature sensor 140 may be formed of a metal such as chromium layer / platinum layer (Cr / Pt).
  • FIG. 26 illustrates a calibration curve of the temperature sensor of FIG. 25.
  • the resistance of the temperature sensor increases from about 820 ⁇ to about 880 ⁇ .
  • the temperature of a sweat can be measured by measuring the electrical resistance of the temperature sensor according to a temperature change.
  • the sweat contains metabolic secretions such as lactic acid so that the sweat pH may be lowered within the range of 4-6. If the actual value of glucose concentration is the same as the measured value by the glucose sensor at pH 5, the measured value of glucose concentration may be lower than the actual value at pH 4, and the measured value of glucose concentration is lower than the actual value at pH 6 and pH 7. Can be large.
  • the measured value of glucose concentration is corrected when the pH is changed while the glucose concentration in sweat is kept constant at 0.3 mM.
  • the measured value of glucose concentration becomes smaller than the actual value of 0.3mM.
  • the pH is increased from 5 to 6, the measured value of glucose becomes larger than the actual value of 0.3mM, so the measured value is lowered to It can be calibrated to 0.3mM. In this way, the glucose concentration can be accurately measured by correcting the glucose concentration measured by the glucose sensor in real time according to the change of pH.
  • 29 to 38 illustrate a method of forming a biosensor according to an embodiment of the present invention.
  • 29, 31, 33, 35, and 37 show perspective views of the biosensing device during the formation process
  • FIGS. 30, 32, 34, 36, and 38 are cross-sectional views of regions of the perspective view.
  • the first region A represents a region in which the humidity sensor is formed
  • the second region B represents a region in which the glucose sensor is formed
  • the third region C represents an region in which the pH sensor is formed
  • the fourth region Region D represents the region in which the temperature sensor is formed.
  • a first insulating layer 161 is formed on the sacrificial substrate 500.
  • the sacrificial substrate 500 may be, for example, a silicon substrate.
  • the first insulating layer 161 may be formed, for example, by spin coating polyimide.
  • the wiring pattern 150 is formed on the first insulating layer 161.
  • the wiring pattern 150 may include a first wiring pattern 151, a second wiring pattern 152, a third wiring pattern 153, and a fourth wiring pattern 154.
  • the wiring pattern 150 may be formed of a conductive material, for example, a metal such as gold (Au), platinum (Pt), aluminum (Al), nickel (Ni), or a metal oxide such as ITO.
  • the wiring pattern 150 may be formed of a double layer such as a chromium layer / gold layer (Cr / Au).
  • the wiring pattern 150 may be formed by sequentially patterning a chromium layer and a gold layer on the first insulating layer 161.
  • the wiring pattern 150 may be formed to have a serpentine shape.
  • the fourth wiring patterns 154 are separated from each other in the fourth region D without being connected to each other.
  • the second electrode 122 of the glucose sensor is formed in the second region B, and the temperature sensor 140 is formed in the fourth region D.
  • the second electrode 122 and the temperature sensor 140 of the glucose sensor may perform a physical vapor deposition process such as sputtering on the first insulating layer 161 on which the wiring pattern 150 is formed, to thereby form a chromium layer and a platinum layer. It can be formed at the same time by sequentially forming and then patterning.
  • the second electrode 122 of the glucose sensor is formed on the second wiring pattern 152, and the temperature sensor 140 is formed on the first insulating layer 161.
  • the temperature sensor 140 is formed to connect the fourth wiring patterns 154 separated from each other.
  • a second insulating layer 162 covering the wiring pattern 150 is formed on the sacrificial substrate 500.
  • the second insulating layer 162 is formed by spin coating an epoxy layer on the first insulating layer 161 on which the second electrode 122 and the temperature sensor 140 of the glucose sensor are formed to form an epoxy layer. By patterning the layer. When the epoxy layer is patterned, the first insulating layer 161 may also be patterned to be removed in areas other than the wiring pattern 150 and the temperature sensor 140. By the patterning, the first insulating layer 161 and the second insulating layer 162 may have a serpentine shape.
  • the second insulating layer 162 exposes the first region A, the second region B, the third region C, and the terminal region of the wiring pattern 150.
  • the second insulating layer 162 may cover the temperature sensor 140 without exposing it.
  • the resultant on the sacrificial substrate 500 formed up to the second insulating layer 162 is transferred to the support layer 160.
  • the resultant may be transferred to the support layer 160 by a water soluble tape, and the water soluble tape may be removed by water after the transfer.
  • the humidity sensor 140 is formed on the first wiring pattern 151 of the first region A.
  • the humidity sensor 110 may include a first electrode 111 and a second electrode 112.
  • the first electrode 111 and the second electrode 112 of the humidity sensor 110 may be formed on the first wiring pattern 151 electrically separated from each other.
  • the humidity sensor 110 provides an acetonitrile solution containing 0.01 M of 3,4-ethylenedioxythiophene and 0.1 M of LiClO 4 to the first region A to perform an electroplating process.
  • the third electrode 123 of the glucose sensor 120 is formed on the second wiring pattern 152 of the second region B, and the pH sensor 130 is formed on the third wiring pattern 153 of the third region C. To form a second electrode 132.
  • the third electrode 123 of the glucose sensor 120 and the second electrode 132 of the pH sensor 130 may be formed of, for example, a silver layer / silver chloride layer (Ag / AgCl).
  • the silver layer may be formed by performing an electroplating process by providing an aqueous solution of 5 mM AgNO 3 and 1 M KNO 3 in the second region B and the third region C.
  • the silver chloride layer may be formed by providing an aqueous solution of 0.1M KCl and 0.01M HCl in a region where the silver layer is formed and chlorinating the upper portion of the silver layer by performing an electroplating process.
  • the first electrode 121 of the glucose sensor 120 is formed on the second wiring pattern 152.
  • the first electrode 121 may include a porous gold layer 121a, a hydrogen peroxide decomposition layer 121b, and a glucose decomposition layer 121c.
  • the porous gold layer 121a may be formed by performing an electroplating process by providing a 2 M sulfuric acid aqueous solution containing 2 mM HAuCl 4 in the second region B.
  • the hydrogen peroxide decomposition layer 121b includes 10 mM KCl, 2.5 mM K 3 [Fe (CN) 6 ], and 2.5 mM FeCl 3 ⁇ 6H 2 O in the second region B in which the porous gold layer 121a is formed. It may be formed by depositing a Prussian blue on the porous gold layer 121a by providing an aqueous solution of hydrochloric acid of 0.1M and performing an electroplating process.
  • the glucose degradation layer 121c may be formed by fixing glucose oxidase (GOx) to the hydrogen peroxide decomposition layer 121b.
  • GOx glucose oxidase
  • chitosan is dissolved in 2 wt% acetic acid to form a 1 wt% chitosan solution.
  • the chitosan solution is mixed with IX PBS (phosphate buffered saline) containing exfoliated graphite to form a chitosan-graphene mixed solution.
  • IX PBS phosphate buffered saline
  • Glucose oxidase and BSA bovine serum albumin
  • Glucose oxidase and BSA bovine serum albumin
  • glucose oxidase is added to the chitosan-graphene mixed solution to a concentration of 0.05 g / mL to form a GOx mixed solution.
  • 0.8 ⁇ l of the GOx-BSA mixed solution is dropped on the porous gold layer 121a and then dried. Subsequently, 0.8 ⁇ l of the GOx mixed solution is dropped on the porous gold layer 121a and dried. As a result, the glucose decomposition layer 121c is formed.
  • the first electrode 121, the second electrode 122, and the third electrode 123 of the glucose sensor 120 may be formed on the second wiring pattern 152 electrically separated from each other.
  • the first electrode 131 of the pH sensor 130 is formed on the third wiring pattern 153 of the third region C.
  • the first electrode 131 of the pH sensor 130 may be formed of polyaniline by performing an electroplating process by providing an aqueous solution of 1M hydrochloric acid containing 0.1M aniline in the third region C. Can be.
  • the first electrode 131 and the second electrode 132 of the pH sensor 130 may be formed on the third wiring pattern 153 that is electrically separated from each other.
  • the screen layer 170 is formed on the glucose sensor 120 in the second region B.
  • the screen layer 170 may be formed by drop casting 2 ⁇ l of 0.5 wt% Nafion onto the glucose sensor 120.
  • the sweat absorption layer 180 covering the biosensor 100 is formed on the screen layer 170.
  • Sweat absorbing layer 180 may be formed of a porous material, for example, a fibrous material such as cotton can absorb and discharge sweat well.
  • the waterproof layer 190 is formed below the support layer 160.
  • the waterproof layer 190 may be formed of, for example, Tegaderm or the like.
  • the order of forming the components of the biosensing device 10 is not limited to the order described above and can be changed.
  • FIG. 39 is a plan view of a biosensor according to another embodiment of the present invention
  • FIG. 40 is an exploded perspective view of the biosensor of FIG. 39
  • FIG. 41 is a front view of the biosensor of FIG. 39
  • FIG. 42 is a view of FIG. 39. Represents a real image of the bio sensing device.
  • the biosensor 20 may include a biosensor 200, a wiring pattern 250, a support layer 260, an insulation layer 262, a spacer 265, a screen layer 270, And a cover layer 280.
  • a description of a portion overlapping with the biosensor 100 of the biosensor 10 described above may be omitted.
  • the biosensor 200 may include a glucose sensor 220, a pH sensor 230, and a temperature sensor 240.
  • the wiring pattern 250 may include a first wiring pattern 251, a second wiring pattern 252, and a third wiring pattern 253.
  • the first wiring pattern 52 may be disposed along one side of the support layer 260
  • the second wiring pattern 252 may be disposed along the other side of the support layer 260.
  • Each of the third wiring patterns 253 may be disposed on one side and the other side of the support layer 260.
  • the wiring pattern 250 may be formed of a conductive material, for example, a metal such as gold (Au), platinum (Pt), aluminum (Al), nickel (Ni), or a metal oxide such as ITO.
  • the wiring pattern 250 may be formed of a double layer such as a chromium layer / gold layer (Cr / Au).
  • the glucose sensor 220 may include a first electrode 221, a second electrode 222, and a third electrode 223.
  • the first electrode 221 may be a working electrode
  • the second electrode 222 may be a counter electrode
  • the third electrode 223 may be a reference electrode.
  • the glucose sensor 220 is a three-electrode sensor, but is not limited thereto, and may be formed as a two-electrode sensor.
  • the first electrode 221, the second electrode 222, and the third electrode 223 of the glucose sensor 220 may be disposed on the first wiring pattern 251 electrically separated from each other.
  • the glucose sensor 220 may be electrically connected to an external device by the first wiring pattern 251.
  • the glucose sensor 220 measures glucose concentration in the sweat.
  • the glucose sensor 220 has a structure in which the second electrode 222 and the third electrode 223 surround the first electrode 221 so that not only the glucose sensor 220 but also the entire biosensor 20 may be highly integrated. Can be.
  • the first electrode 221 may be formed in a small size having a diameter of about 1,000 ⁇ m or less, thereby accurately measuring the glucose concentration in the sweat even with a small amount of sweat.
  • the pH sensor 230 may include a first electrode 231 and a second electrode 232.
  • the first electrode 231 may be a working electrode
  • the second electrode 232 may be a reference electrode and / or a counter electrode.
  • the first electrode 231 may be a reference electrode and / or a counter electrode
  • the second electrode 232 may be a working electrode.
  • the pH sensor 230 is a two-electrode sensor, but is not limited thereto, and may be formed of a three-electrode sensor such as the glucose sensor 220.
  • the first electrode 231 and the second electrode 232 of the pH sensor 230 may be disposed on the second wiring pattern 252 electrically separated from each other.
  • the pH sensor 230 may be electrically connected to the external device by the second wiring pattern 252.
  • the pH sensor 230 measures the pH of the sweat.
  • the pH sensor 230 may measure the pH of the sweat by measuring a change in the open circuit potential (OCP) between the first electrode 231 and the second electrode 232.
  • OCP open circuit potential
  • the glucose concentration measurement value may be corrected in real time according to the pH value measured by the pH sensor 230.
  • the pH sensor 230 may function as two pH sensors by disposing two first electrodes 231 around the second electrode 232. Two first electrodes 231 may surround the second electrode 232.
  • the temperature sensor 240 is disposed on the support layer 260 and connected to the third wiring patterns 253 separated from each other.
  • the temperature sensor 240 may have a serpentine shape.
  • the temperature sensor 240 measures the temperature of the sweat.
  • the temperature sensor 240 may measure a temperature of sweat by measuring an electrical resistance value according to a temperature change as a resistor.
  • the glucose concentration measurement value may be corrected in real time according to the temperature value measured by the temperature sensor 240.
  • the biosensor 200 includes, but is not limited to, a pH sensor 230 and a temperature sensor 240 to measure glucose concentration more accurately.
  • the sensors may not be included or only one may be selected.
  • the support layer 260 is disposed under the biosensor 200 and the wiring pattern 250 to support the biosensor 200 and the wiring pattern 250.
  • the support layer 260 may be formed of a polymer, for example, polyimide.
  • the support layer 260 may be a polymer strip.
  • the insulating layer 262 is disposed on the wiring pattern 250.
  • the insulating layer 262 may be formed of, for example, epoxy or the like.
  • the insulating layer 262 exposes the terminal region of the biosensor 200 and the wiring pattern 250, whereby the biosensor 200 may be in contact with sweat, and the terminal region of the wiring pattern 250 may be external. It may be electrically connected with the device. However, the insulating layer 262 may be covered without exposing the temperature sensor 240.
  • Spacers 265 are disposed on both sides of the support layer 260, respectively.
  • the spacer 265 may be disposed at both sides of an area in which the biosensor 200 is disposed along the direction in which the support layer 260 extends.
  • the spacer 265 may be formed of an adhesive polymer such as, for example, polytetrafluoroethylene (PTFE).
  • An insulating layer 262 may be disposed between the spacer 265 and the support layer 260. Referring to FIG. 35, a capillary force formed by a sweat absorbing gap 265g defined by the support layer 260, the cover layer 280, the insulating layer 262, and the spacer 265 ( Capillary force can absorb sweat.
  • the spacer 265 may have a thickness capable of forming a sweat absorption gap 265g that induces capillary force.
  • Screen layer 270 is disposed over glucose sensor 220.
  • the screen layer 270 may filter out foreign substances (including drugs) that may interfere with sensing glucose from absorbed sweat.
  • the screen layer 270 may stably fix the glucose decomposition layer (121c of FIG. 8) of the first electrode 221 of the glucose sensor 220.
  • the screen layer 270 may be formed of, for example, Nafion.
  • the cover layer 280 is disposed on the biosensor 200 and the spacer 265.
  • the cover layer 280 may form a sweat absorption gap 265g together with the support layer 260 and the spacer 265 to absorb sweat.
  • the cover layer 280 may be formed of, for example, polyethylene terephthalate (PET).
  • the pH sensor 230, the glucose sensor 220, and the temperature sensor 240 may be sequentially disposed in the direction in which the support layer 260 extends between the two spacers 265. Sweat absorbed through the sweat absorption gap 265g may move to the temperature sensor 240 through the pH sensor 230 and the glucose sensor 220.
  • the order of placement of the sensors is not limited and can be changed.
  • the biosensor 200 may not include a humidity sensor because the biosensor 20 directly collects the amount of sweat required for glucose concentration measurement through the sweat absorption gap 265g.
  • the bio-sensing device 20 may absorb the sweat generated in the human body without being attached to the skin and measure the glucose concentration, and may be used for a single use when the glucose concentration measurement is required. As such, the biosensing device 20 may be used without being attached to the skin, thereby eliminating foreign matters and being easy to use.
  • FIG. 43 is a diagram for describing a method of using the biosensing device of FIG. 39.
  • the biosensor 20 may be connected to an external device through the ZIF connector 25, and the glucose concentration may be measured. As such, the biosensing device 20 may be conveniently used for one-time use without being attached to the human body.
  • the cover layer 280 of the bio-sensing device 20 of FIG. 39 may be formed in the same manner as the sweat-absorbing layer 180 of the bio-sensing device 10 described above, or may include a sweat-absorbing layer. . Even if the amount of sweat emitted from the human body is small, the sweat may be absorbed by the cover layer 280 and collected quickly and easily.
  • the biosensing device 20 may further include a waterproof layer disposed under the support layer 260.
  • the waterproof layer may be formed in the same manner as the waterproof layer 190 of the bio-sensing device 10 described above.
  • the bio-sensing device 20 may be fixed to the user's body by the waterproof layer, and after the user's activity is absorbed sufficiently for a certain period of time, the bio-sensing device 20 is separated from the body, and the ZIF connector
  • the glucose concentration can be measured by connecting to an external device through 25. That is, the biosensing device 20 including the waterproof layer may be effectively attached to a user who is less sweaty or less likely to sweat.
  • the waterproof layer may prevent moisture other than sweat from penetrating into the biosensor 200 and may help sweat to be collected into the biosensor 200 region.
  • 44 to 47 illustrate a method of forming a biosensor according to another embodiment of the present invention.
  • the support layer 260 may be formed of a polymer, for example, polyimide, and may be a polyimide strip.
  • the wiring pattern 250 may include a first wiring pattern 251, a second wiring pattern 252, and a third wiring pattern 153.
  • the wiring pattern 250 may be formed of a conductive material, for example, a metal such as gold (Au), platinum (Pt), aluminum (Al), nickel (Ni), or a metal oxide such as ITO.
  • the wiring pattern 250 may be formed of a double layer such as a chromium layer / gold layer (Cr / Au).
  • the wiring pattern 250 may be formed by sequentially patterning a chromium layer and a gold layer on the support layer 260.
  • the third wiring patterns 253 are separated from each other in the region where the temperature sensor is formed without being connected to each other.
  • the second electrode 222 of the glucose sensor is formed on the first wiring pattern 251, and the temperature sensor 240 is formed on the support layer 260.
  • the second electrode 222 and the temperature sensor 240 of the glucose sensor perform a physical vapor deposition process such as sputtering on the support layer 260 on which the wiring pattern 250 is formed to sequentially form a chromium layer and a platinum layer. It can be formed simultaneously by then patterning.
  • the temperature sensor 240 is formed to connect the third wiring patterns 253 separated from each other.
  • an insulating layer 262 is formed on the support layer 260 to cover the wiring pattern 250.
  • the insulating layer 262 is formed by spin coating an epoxy on the support layer 260 on which the second sensor 222 and the temperature sensor 240 of the glucose sensor are formed to form an epoxy layer, and then patterning the epoxy layer. It can be formed by.
  • the insulating layer 262 exposes a region where the glucose sensor and the pH sensor are formed and an end region of the wiring pattern 250.
  • the insulating layer 262 may cover the temperature sensor 240 without exposing it.
  • the first electrode 221 and the third electrode 223 of the glucose sensor 220 are formed on the first wiring pattern 251 exposed by the insulating layer 262.
  • the first electrode 231 and the second electrode 232 of the pH sensor 230 are formed on the second wiring pattern 252 exposed by the insulating layer 262.
  • a description of portions overlapping with the processes of forming the glucose sensor 120 and the pH sensor 130 of the biosensor 10 may be omitted.
  • the first electrode 221 of the glucose sensor 220 may include a porous gold layer, a hydrogen peroxide decomposition layer, and a glucose decomposition layer.
  • the third electrode 223 of the glucose sensor 220 and the second electrode 232 of the pH sensor 230 may be formed of, for example, a silver layer / silver chloride layer (Ag / AgCl).
  • the first electrode 231 of the pH sensor 230 may be formed of, for example, polyaniline.
  • the first electrode 221, the second electrode 222, and the third electrode 223 of the glucose sensor 220 may be formed on the first wiring pattern 251 electrically separated from each other, and the pH sensor 230.
  • the first electrode 231 and the second electrode 232 may be formed on the second wiring pattern 252 electrically separated from each other.
  • Spacers 265 are formed on both sides of the support layer 260, respectively.
  • the spacer 265 may be formed at both sides of an area where the biosensor 200 is disposed along the direction in which the support layer 260 extends.
  • the spacer 265 may be formed of an adhesive polymer such as, for example, PTFE.
  • An insulating layer 262 may be disposed between the spacer 265 and the support layer 260.
  • the screen layer 270 is formed on the glucose sensor 220.
  • the screen layer 270 may be formed of, for example, Nafion. After the screen layer 270 is formed, glutaraldehyde is dropped cast on the glucose sensor 220 to crosslink the glucose decomposition layer.
  • the cover layer 280 is formed on the biosensor 200 and the spacer 265.
  • the cover layer 280 may be formed of, for example, PET.
  • the cover layer 280 may form a sweat absorption gap 265g together with the support layer 260 and the spacer 265 to absorb sweat.
  • the order of forming the components of the biosensing device 20 is not limited to the order described above and may be changed.
  • the cover layer 280 may be formed of a porous material, for example, a fibrous material such as cotton can absorb and discharge sweat well.
  • the waterproof layer may be formed under the support layer 260.
  • the waterproof layer may be formed of, for example, Tegaderm.
  • FIG. 48 is a perspective view of the drug delivery device according to one embodiment of the present invention
  • FIG. 49 is an exploded perspective view of the drug delivery device of FIG. 48
  • FIG. 50 shows an actual image of the drug delivery device of FIG. 48
  • FIG. 51 is Partial enlarged view of a drug delivery unit according to an embodiment of the present invention
  • Figure 52 shows a phase change nanoparticles according to an embodiment of the present invention.
  • the drug delivery device 30 may include a drug delivery unit 300 and a heating unit 350.
  • the drug delivery unit 300 may include a microneedle bonding layer 310, a microneedle 320, a phase change layer 330, and a phase change nanoparticle 340.
  • the microneedle bonding layer 310 may be combined with the microneedle 320 to support the microneedle 320.
  • the microneedle 320 may be arranged in two dimensions on the microneedle bonding layer 310.
  • the microneedle bonding layer 310 and the microneedle 320 may be integrally formed using the same material, and the microneedle bonding layer 310 may stably support the microneedle 320.
  • the microneedle bonding layer 310 and the microneedle 320 may be formed of, for example, hyaluronic acid hydrogel.
  • the surface of the microneedle 320 may be coated with the phase change layer 330.
  • the phase change layer 330 may be formed of a material capable of causing phase change at a predetermined temperature or higher, for example, tetradecanol.
  • tetradecanol a material capable of causing phase change at a predetermined temperature or higher, for example, tetradecanol.
  • the glucose control drug 341 stored in the phase change nanoparticles 340 inside the microneedle 320 may be released to the outside. It becomes the state that I can.
  • the phase change nanoparticle 340 may include a first phase change nanoparticle 340a and a second phase change nanoparticle 340b.
  • the phase change nanoparticle 340 may include a glucose regulating drug 341, a phase change material 342, and a ligand compound 343.
  • the glucose regulating drug 341 may include, for example, metformin, chlorpropamide, or the like.
  • the phase change material 342 may have a spherical shape and store a glucose regulating drug 341 therein.
  • the phase change material 342 may include a material that may undergo phase change at a predetermined temperature or higher, for example, palm oil, tridecanoic acid, or the like.
  • the first phase change nanoparticle 340a may include a phase change material, for example, palm oil, in which a phase change occurs at a first phase change temperature, and the second phase change nanoparticle 340b may have a second phase change. Phase change material, such as tridecanoic acid, in which phase change may occur at temperature.
  • the first phase change temperature may be lower than 40 ° C., for example 38 ° C.
  • the second phase change temperature may be higher than 40 ° C., for example 43 ° C.
  • the first phase change nanoparticle 340a and the second phase change nanoparticle 340b may release the glucose regulating drug 341 by causing a phase change of the phase change material 342 at different temperatures.
  • the first phase change nanoparticle 340a having a phase change temperature lower than 40 ° C. releases the glucose regulating drug 341, and the phase change temperature is higher than 40 ° C.
  • the second phase change nanoparticle 340b having a high change temperature does not release the glucose regulating drug 341.
  • both the first phase change nanoparticle 340a and the second phase change nanoparticle 340b having a phase change temperature lower than 45 ° C. are glucose control drugs 341. ).
  • the user may effectively control glucose in the human body.
  • Ligand compound 343 is a substance capable of forming an oil-in-water emulsion, for example DOPA-HA (3,4-Dihydroxyl-L-phenylalanine (DOPA) -conjugated hyaluronic acid) And poloxamers.
  • Ligand compound 343 may surround phase change material 342, allowing phase change nanoparticles 340 to be uniformly dispersed within microneedle 320.
  • the heating unit 350 may include a heater 370, a temperature sensor 380, a support layer 360, a first insulating layer 361, a second insulating layer 362, and a waterproof layer 390.
  • One or more heaters 370 may be included in the heating unit 350.
  • the heating area of the heating unit 350 may be divided according to the number of heaters 370.
  • the heater 370 may include a first heater 371, a second heater 372, and a third heater 373, and the heating unit 350 may be divided into three heating regions. have. For example, when the drug delivery unit 300 is heated to 40 ° C.
  • the first phase change particles 340a in the microneedle 320 disposed on the first heater 371 are Phase change to release the glucose control drug (341), when operating the first heater 371 to heat the drug delivery unit 300 to 45 °C in the microneedle 320 disposed on the first heater 371
  • the second phase change particle 340b phase changes to release the glucose regulating drug 341.
  • the first phase change particle 340a in the microneedle 320 disposed on the second heater 372 is phase changed.
  • the phase change particle 340b phase changes to release the glucose regulating drug 341.
  • the first phase change particle 340a in the microneedle 320 disposed on the third heater 373 is phase changed.
  • the second in the microneedle 320 disposed on the third heater 373 changes to release the glucose regulating drug 341.
  • the release of the glucose regulating drug 341 may be controlled by controlling the operations of the first heater 371, the second heater 372, and the third heater 373. Therefore, the user can effectively adjust the dose of the glucose regulating drug 341 injected into the human body according to the measured glucose concentration.
  • the glucose regulating drug 341 since the glucose regulating drug 341 may be repeatedly injected into the drug delivery device 30 once attached to the human body, it may be used for a long time and the convenience may be increased.
  • the temperature sensor 380 may be disposed adjacent to the heater 370 to measure the temperature.
  • the temperature sensor 380 may be disposed between the first heater 371 and the second heater 372 and between the second heater 372 and the third heater 373.
  • the temperature sensor 380 may confirm whether the heater 370 is in operation and may control the heater 370.
  • the support layer 360 is disposed under the heater 370 and the temperature sensor 380 to support the heater 370 and the temperature sensor 380.
  • the support layer 360 may be combined with the drug delivery unit 300 to support the drug delivery unit 300.
  • the support layer 360 may be formed of a silicone polymer, for example, polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • the support layer 360 may be a silicon patch.
  • the first insulating layer 361 is disposed between the heater 370 and the support layer 360 and between the temperature sensor 380 and the support layer 360, and the second insulating layer 362 is the heater 370 and the drug delivery unit. Between 300 and between the temperature sensor 380 and the drug delivery unit 300.
  • the first insulating layer 361 and / or the second insulating layer 362 may have a serpentine shape and may have elasticity.
  • the first insulating layer 361 and the second insulating layer 362 may be formed of, for example, polyimide, epoxy, or the like.
  • the second insulating layer 362 exposes the distal regions of the heater 370 and the temperature sensor 380, whereby the distal regions of the heater 370 and the temperature sensor 380 may be electrically connected to an external device. .
  • the waterproof layer 390 is disposed below the support layer 360.
  • the waterproof layer 390 may prevent foreign substances such as moisture from penetrating into the drug delivery device 30 after the drug delivery device 30 is attached to the human body, and the glucose control drug released from the drug delivery unit 300 ( 341) can be prevented from being discharged to the outside.
  • the waterproof layer 390 may be formed of, for example, Tegaderm.
  • 53 to 55 illustrate a method of forming a drug delivery unit according to an embodiment of the present invention.
  • a hyaluronic acid solution 300s including phase change nanoparticles loaded with a glucose control drug in a mold 600 is provided.
  • the mold 600 has a groove 600h arranged two-dimensionally.
  • the groove 600h may have a diameter of about 250 ⁇ m and a height of about 1 mm.
  • the mold 600 may be, for example, a PDMS mold.
  • the hyaluronic acid solution 300s provided in the mold 600 is cured to form the microneedle bonding layer 310 and the microneedle 320.
  • the microneedle bonding layer 310 and the microneedle 320 may be integrally formed.
  • the microneedle 320 is formed in the groove 600h of the mold 600, and is arranged two-dimensionally in the microneedle bonding layer 310.
  • the microneedle 320 may have a diameter of about 250 ⁇ m and a height of about 1 mm.
  • the microneedle bonding layer 310 and the microneedle 320 are separated from the mold 600.
  • the microneedle bonding layer 310 and the microneedle 320 may be separated from the mold 600 by attaching a heating part 350 to the microneedle bonding layer 310.
  • the drug delivery unit may be completely formed and then combined with the heating unit.
  • the surface of the microneedle 320 is coated with a phase change material 330s.
  • the surface of the microneedle 320 may be coated with a phase change material 330s by performing a process such as spray coating, dip coating, or drop casting.
  • the phase change material 330s may be, for example, tetradecanol.
  • FIG. 56 illustrates a wearable bio system according to an embodiment of the present invention.
  • the wearable bio system 1 may include a bio sensing device 10, a drug delivery device 30, and a control device 40. Since the biosensing device 10 and the drug delivery device 30 are the same as the biosensing device and the drug delivery device described in the above-described embodiments, the overlapping description may be omitted.
  • the bio sensing device 10 may include a bio sensing communication unit 11, the drug delivery device 30 may include a drug delivery communication unit 31, and the control device 40 may control the control communication unit 41. It may include.
  • the bio-sensing communication unit 11, the drug delivery communication unit 31, and the control communication unit 41 may be connected to each other at least two by wire or wirelessly, and may transmit and receive electrical signals to each other.
  • the control device 40 may transmit and receive an electrical signal with the biosensing device 10 and the drug delivery device 30, and may control the biosensing device 10 and the drug delivery device 30.
  • control device 40 is illustrated separately from the bio-sensing device 10 and the drug delivery device 30, but is not limited thereto.
  • the control device 40 may include the bio-sensing device 10 or the drug delivery device ( 30).
  • the wearable bio system 1 may include the strip type bio sensing device 20 of FIG. 39 instead of the patch type bio sensing device 10 of FIG. 1.
  • the control device 40 measures the humidity by collecting a signal from the humidity sensor 110 to determine whether a certain amount of sweat is absorbed before analyzing the glucose concentration in the human body.
  • the control device 40 collects a signal from the glucose sensor 120 to measure the glucose concentration in the sweat. In addition, the control device 40 collects a signal from the pH sensor 130 to measure the pH of the sweat, and collects a signal from the temperature sensor 140 to measure the temperature of the sweat.
  • the control device 40 corrects the measured glucose concentration value by using the measured pH value and the temperature value.
  • signals may be distorted due to changes in pH or temperature, thereby causing measurement errors.
  • the control device 40 may more accurately correct the measured glucose concentration value by using the measured pH value and the temperature value.
  • the biosensor 100 may further include a strain sensor, and may correct signal distortion that may be caused by a user's movement.
  • the control device 40 diagnoses the blood glucose state of the user according to the corrected glucose concentration.
  • control device 40 may operate the drug delivery device 30 to inject the glucose regulating drug 341 into the human body.
  • the drug delivery unit 300 includes a phase change nanoparticle 340 loaded with a glucose control drug 341, and the phase change nanoparticle 340 has first phase change nanoparticles 340a having different phase change temperatures. And a second phase change nanoparticle 340b. Therefore, by adjusting the heating temperature of the drug delivery unit 300 it is possible to adjust the dose of the glucose control drug (341).
  • the heating unit 350 includes a heater 370 for heating the drug delivery unit 300, and the heater 370 includes two or more separate heaters, for example, the first heater 371 and the second heater ( 372, and a third heater 373.
  • the operation of the first heater 371, the second heater 372, and the third heater 373 may be controlled to adjust the drug injection region of the drug delivery unit 300.
  • the process of glucose regulation can be repeated over and over in real time. Thereby, the glucose in the human body of the user can be kept constant.
  • control device 40 may determine the user's status diagnosed through the control communication unit 41 or a separate network device connected to the control communication unit 41, the user's wireless terminal or the family's wireless terminal, a specific hospital It can be sent to a first aid center or service provider, and managed so that the user's status is not at risk.
  • the biosensing device according to embodiments of the present invention may have excellent reliability.
  • the bio-sensing device can accurately diagnose disease or measure biological signals.
  • the biosensing device may be highly integrated.
  • the biosensor included in the biosensor may be miniaturized so that a plurality of various sensors may be integrated in a small area.
  • the biosensing device may have elasticity and be attached to a human body.
  • the bio-sensing device may have elasticity that can maintain reliability even when deformed by a user's operation.
  • the bio-sensing device is attached to the human body to perform diagnosis and measurement on the human body in real time, and is effective and convenient to use, so anyone can use it easily.
  • Biosensing device can accurately measure the glucose concentration of the human body in a non-invasive manner.
  • the bio-sensing device can measure glucose concentration in sweat.
  • a biosensor such as a glucose sensor included in the biosensing device, can be miniaturized so that the glucose concentration can be accurately measured even with a small amount of sweat.
  • the glucose sensor may include a porous gold layer having a large electrochemically active surface so that glucose concentration can be accurately measured even with a small amount of sweat.
  • the bio-sensing device may check whether sweat collected for glucose sensing is collected by a humidity sensor.
  • the biosensing device can measure the glucose concentration more accurately by measuring the glucose concentration measured by the glucose sensor by the pH sensor and / or the temperature sensor.
  • the bio-sensing device can easily and efficiently collect the sweat necessary for sensing by the sweat-absorbing layer.
  • the bio-sensing device may remove foreign substances from sweat used for glucose sensing by the screen layer.
  • the bio-sensing device can prevent the sweat used for glucose sensing from being discharged to the outside by the waterproof layer, and prevent foreign substances such as external moisture that prevents glucose sensing from penetrating into the bio-sensing device.
  • the biosensing device according to the embodiments of the present invention may be used for a single use.
  • the bio-sensing device can be miniaturized into a strip shape and can easily collect sweat through a sweat absorption gap, and thus can be conveniently used for a single use.
  • the bio-sensing device can collect sweat more easily by forming a cover layer as a sweat absorbing layer.
  • the bio-sensing device may be used by attaching to the human body by including a waterproof layer, and may be effectively attached to a user who has little sweat or does not sweat well.
  • Drug delivery device can inject drugs into the human body.
  • the drug delivery device may adjust the amount of drug injected into the human body.
  • the drug delivery device may sequentially inject drugs step by step according to the user's condition.
  • the drug delivery device may inject glucose control drugs into the human body.
  • the drug delivery device may adjust the amount of glucose regulating drug injected into the human body according to the glucose concentration in the human body of the user.
  • the drug delivery device may sequentially release the glucose regulating drug step by step, thereby allowing the user to effectively regulate glucose in the human body.
  • the drug delivery device may be repeatedly used to release the glucose control drug several times after being attached to the human body, and thus may be used for a long time.

Abstract

L'invention concerne un dispositif de biodétection et un dispositif d'administration de médicament. Un dispositif de biodétection, selon un mode de réalisation de la présente invention, comprend : une couche de support ; et un biocapteur disposé sur la couche de support. Un dispositif de biodétection, selon un autre mode de réalisation de la présente invention, comprend : une couche de support ; des entretoises disposées des deux côtés de la couche de support ; un biocapteur disposé sur la couche de support entre les entretoises ; et une couche de couverture disposée sur les entretoises de sorte à être espacée du biocapteur. Un dispositif d'administration de médicament, selon un autre mode de réalisation de la présente invention, comprend : une micro-aiguille ; et une partie d'administration de médicament disposée dans la micro-aiguille et contenant des nanoparticules à changement de phase chargées de médicament. Le dispositif d'administration de médicament peut en outre comprendre une partie chauffante accouplée à la partie d'administration de médicament pour chauffer la partie d'administration de médicament.
PCT/KR2017/006572 2016-06-29 2017-06-22 Dispositif de biodétection et dispositif d'administration de médicament WO2018004191A1 (fr)

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KR1020160081447A KR101933760B1 (ko) 2016-06-29 2016-06-29 바이오 센싱 장치
KR10-2016-0081453 2016-06-29
KR10-2016-0081447 2016-06-29
KR1020160081453A KR101789716B1 (ko) 2016-06-29 2016-06-29 바이오 센싱 장치
KR1020160081450A KR101843263B1 (ko) 2016-06-29 2016-06-29 약물 전달 장치

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