KR20160144069A - Graphene bioelectronic device - Google Patents

Graphene bioelectronic device Download PDF

Info

Publication number
KR20160144069A
KR20160144069A KR1020150080349A KR20150080349A KR20160144069A KR 20160144069 A KR20160144069 A KR 20160144069A KR 1020150080349 A KR1020150080349 A KR 1020150080349A KR 20150080349 A KR20150080349 A KR 20150080349A KR 20160144069 A KR20160144069 A KR 20160144069A
Authority
KR
South Korea
Prior art keywords
layer
graphene
bioelectronic device
sensor
metal oxide
Prior art date
Application number
KR1020150080349A
Other languages
Korean (ko)
Other versions
KR101789711B1 (en
Inventor
김대형
현택환
최승홍
이현재
송창영
이영식
Original Assignee
서울대학교산학협력단
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.)
Filing date
Publication date
Application filed by 서울대학교산학협력단, 기초과학연구원 filed Critical 서울대학교산학협력단
Priority to KR1020150080349A priority Critical patent/KR101789711B1/en
Priority to PCT/KR2016/005950 priority patent/WO2016200105A2/en
Publication of KR20160144069A publication Critical patent/KR20160144069A/en
Application granted granted Critical
Publication of KR101789711B1 publication Critical patent/KR101789711B1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00064—Constructional details of the endoscope body
    • C01B31/0438—

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Optics & Photonics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Materials Engineering (AREA)

Abstract

A graphene bioelectronic device is provided. The graphene bioelectronic device includes a graphene composite layer including at least two graphene layers. The graphene composite layer may include a first graphene layer, a silver nanowire layer disposed on the first graphene layer, and a second graphene layer disposed on the silver nanowire layer.

Description

{GRAPHENE BIOELECTRONIC DEVICE}

The present invention relates to graphene bioelectronic devices.

Recently, gastrointestinal diseases such as colorectal cancer are increasing for various reasons such as stress and irregular eating habits. Improved endoscopes combining imaging and therapy within the gastrointestinal tract for the diagnosis and treatment of gastrointestinal diseases have been proposed. However, such endoscopes are difficult to detect, diagnose, and treat in multimodality at sufficient resolution to detect and treat malformations and cancers.

In order to solve the above problems, the present invention provides a transparent graphene bioelectronic device.

The present invention provides a graphene bioelectronic device having excellent physical properties.

The present invention provides a graphene bioelectronic device having excellent therapeutic and diagnostic effects.

The present invention provides a graphene bioelectronic device that can be highly integrated into an endoscope.

Other objects of the present invention will become apparent from the following detailed description and the accompanying drawings.

A graphene bioelectronic device according to embodiments of the present invention includes a graphene composite layer including two or more graphene layers.

The graphene composite layer may include a first graphene layer, a silver nanowire layer disposed on the first graphene layer, and a second graphene layer disposed on the silver nanowire layer.

The graphene bioelectronic device may further include a plurality of metal oxide layers disposed on the second graphene layer. The metal oxide layer may include an iridium oxide layer.

The graphene bioelectronic device may further include a metal doping layer disposed between the second graphene layer and the metal oxide layer. The metal doping layer may include a gold doping layer.

The graphene bioelectronic device may further include a sensor and an ablation electrode formed by the graphene composite layer and the metal oxide layer. The sensor may include at least one of a tumor sensor, a touch sensor, and a viability sensor. Wherein the tumor sensor comprises a working electrode and a counter electrode, the working electrode comprises the graphene composite layer and the metal oxide layer, the counter electrode comprises the graphene composite layer, do not include.

The graphene bioelectronic device may further comprise a temperature sensor comprising only a patterned portion of the second graphene layer.

The graphene bioelectronic device may be used attached to a camera of an endoscope.

A graphene bioelectronic device according to another embodiment of the present invention includes a first protective layer, a first graphene layer disposed on the first protective layer, a silver nanowire layer disposed on the first graphene layer, A second graphene layer disposed over the second graphene layer, and a second protective layer disposed over the second graphene layer.

The first passivation layer and the second passivation layer may be formed of transparent epoxy.

The graphene bioelectronic device may further include a metal oxide layer disposed on the second graphene layer, the second protective layer exposing at least a portion of the second graphene layer, And may be disposed on an exposed portion of the second graphene layer.

The graphene bioelectronic device may further include a metal doping layer disposed between the second graphene layer and the metal oxide layer.

The graphene bioelectronic device according to embodiments of the present invention may be disposed at an endoscope tip portion to perform a function of diagnosing and treating the inside of a living body. The graphene bioelectronic device can be placed on the camera with high transparency. Thereby, the graphene bioelectronic device can be placed in the endoscope without increasing the surface area of the endoscope tip, and the endoscope system can be highly integrated. Graphene bioelectronic devices provide continuous and accurate tumor sensing and pH sensing, and ablation therapy and feedback monitoring enable excellent therapeutic and diagnostic efficacy. The graphene bioelectronic device can be formed as an ultra thin film and can have excellent mechanical deformation capacity and excellent mechanical stability. In addition, the graphene bioelectronic device can have excellent thermal stability and electrical stability.

Therapeutic diagnostic nanoparticles according to the embodiments of the present invention can be combined treatment of photodynamic therapy, photothermal therapy, and chemotherapy, and thus have excellent therapeutic effects. It is possible to control the release of the chemical drug loaded on the therapeutic diagnostic nanoparticles, thus enabling targeted treatment and minimizing side effects. In addition, additional diagnosis by imaging of cancer cells and the like is possible, and the therapeutic effect can be improved by active targeting.

According to embodiments of the present invention, by adopting a transparent graphene bioelectronic device, a highly integrated endoscope system having excellent therapeutic and diagnostic effects can be realized. The endoscopic system can optimize treatment and diagnostic effects by controlling activation of the therapeutic diagnostic nanoparticles by a red laser and a near infrared laser.

1 schematically shows an endoscope system according to embodiments of the present invention.
Figure 2 shows a top view of a graphene bioelectronic device according to embodiments of the present invention.
3 is a cross-sectional view taken along line I-I 'of Fig.
4 to 10 illustrate a method of manufacturing a graphene bioelectronic device according to embodiments of the present invention.
11 schematically shows a flow chart of a manufacturing process of a graphene bioelectronic device according to an embodiment of the present invention.
12 illustrates the effect of gold doping in the fabrication process of a graphene bioelectronic device according to an embodiment of the present invention.
Figure 13 schematically illustrates the therapeutic diagnostic nanoparticles according to embodiments of the present invention.
14 shows the structure and manufacturing process of the therapeutic diagnostic nanoparticles according to an embodiment of the present invention.
Figure 15 shows the in vivo toxicity test results of the therapeutic diagnostic nanoparticles according to one embodiment of the present invention.
16 shows a schematic structure and a corresponding image of an endoscope system according to an embodiment of the present invention.
17 shows the integration process of the graphene bioelectronic device on the endoscope.
18 shows an external connection of a graphene bioelectronic device installed on an endoscope.
Figure 19 illustrates the transparency and detail design of a graphene bioelectronic device in accordance with an embodiment of the present invention.
Figure 20 shows the thermal stability of a graphene bioelectronic device according to an embodiment of the present invention.
Figure 21 shows the mechanical stability of a graphene bioelectronic device according to an embodiment of the present invention.
22 illustrates material properties of a graphene bioelectronic device according to an embodiment of the present invention.
23 shows the electrical stability of a graphene bioelectronic device according to an embodiment of the present invention.
24 shows tumor sensing characteristics of a graphene bioelectronic device according to an embodiment of the present invention.
25 shows the pH sensing characteristic of a graphene bioelectronic device according to an embodiment of the present invention.
26 shows high frequency ablation characteristics of a graphene bioelectronic device according to an embodiment of the present invention.
27 illustrates contact sensing and temperature sensing characteristics of a graphene bioelectronic device according to an embodiment of the present invention.
28 shows the cell viability sensing characteristic of a graphene bioelectronic device according to an embodiment of the present invention.
Figure 29 shows the targeting, imaging, and therapeutic properties of therapeutic diagnostic nanoparticles in accordance with one embodiment of the present invention.
30 schematically shows a tumor treatment process using an endoscopic system according to an embodiment of the present invention.
31 is a view for explaining in vivo colorectal cancer treatment using an endoscope system according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail with reference to examples. The objects, features and advantages of the present invention will be easily understood by the following embodiments. The present invention is not limited to the embodiments described herein, but may be embodied in other forms. The embodiments disclosed herein are provided so that the disclosure may be thorough and complete, and that those skilled in the art will be able to convey the spirit of the invention to those skilled in the art. Therefore, the present invention should not be limited by the following examples.

Although the terms first, second, etc. 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 each other. In addition, when an element is referred to as being on another element, it may be directly formed on the other element, or a third element may be interposed therebetween.

The sizes of the elements in the figures, or the relative sizes between the elements, may be exaggerated somewhat for a clearer understanding of the present invention. In addition, the shape of the elements shown in the drawings may be somewhat modified by variations in the manufacturing process or the like. Accordingly, the embodiments disclosed herein should not be construed as limited to the shapes shown in the drawings unless specifically stated, and should be understood to include some modifications.

[Endoscopic System]

1 schematically shows an endoscope system according to embodiments of the present invention.

Referring to FIG. 1, the endoscope system 10 may include an endoscope 100 and a graphene bioelectronic device 200.

The endoscope 100 may include a laser providing unit 110, a camera 120, and a saline supplying unit 130. The laser providing unit 110 may provide at least one of a red laser and a near-infrared laser. For example, the laser supplier 110 may simultaneously provide a red laser and a near-infrared laser at the same time. The red laser may have a wavelength of 670 nm, and the near-infrared laser may have a wavelength of 808 nm. The camera 120 may be disposed inside the endoscope 100 to capture a living body such as a large intestine and the captured image may be displayed on a display device (not shown) connected to the endoscope 100. The saline solution provider 130 may provide the saline solution supplied from the outside to clean the tip surface of the endoscope 100 or sterilize and clean the inside of the colon or the like.

The graphene bioelectronic device 200 may be disposed at a tip portion of the endoscope 100 to perform a function of diagnosing and treating the inside of the living body. The graphene bioelectronic device 200 may include an ablation electrode 202 and various sensors such as a tumor sensor 201, a contact sensor 203, a temperature sensor 204, a viability sensor 205, and the like. The graphene bioelectronic device 200 may include a first region A, a second region B, a third region C and a fourth region D and may include sensors 201,203,204, The reference electrode 202 may be separately arranged in the first to fourth regions A, B, C, The graphene bioelectronic device 200 can be placed on the camera 120 with high transparency. Thereby, the graphene bioelectronic device 200 can be placed in the endoscope 100 without increasing the surface area of the endoscope 100, and the endoscope system 10 can be highly integrated.

[ Grapina  Bio-electronics]

FIG. 2 is a plan view of a graphene bioelectronic device according to embodiments of the present invention, and FIG. 3 is a cross-sectional view taken along line I-I 'of FIG.

2 and 3, the graphene bioelectronic device 200 includes various sensors such as a tumor sensor 201, a touch sensor 203, a temperature sensor 204, a viability sensor 205, and an ablation electrode 202 ). The graphene bioelectronic device 200 may include a first region A, a second region B, a third region C, and a fourth region D. [ The ablation electrode 202 may be disposed in the second region B and the contact sensor 203 and the temperature sensor 204 may be disposed in the first region A, 3 region C, and the viability sensor 205 may be disposed in the fourth region D. [ The tumor sensor 201, the ablation electrode 202, the contact sensor 203, the temperature sensor 204, and the survival force sensor 205 can be arranged in the number required for optimization of diagnosis and treatment in the living body, The graphene bio-electronic device 200 may be divided into different regions so as to maximize the transparency thereof.

The graphene bioelectronic device 200 includes a first passivation layer 211, a graphene composite layer 220 and a metal doping layer 231, a metal oxide layer 232 and a second passivation layer 212 can do.

The first protective layer 211 may be disposed below the graphene composite layer 220 to protect and support the graphene composite layer 220. The first passivation layer 211 may be formed of a transparent material such as epoxy.

The graphene composite layer 220 is disposed on the first protective layer 211. The graphene composite layer 220 may include a first graphene layer 221, a silver nanowire layer 222, and a second graphene layer 223. The first graphene layer 221 and the second graphene layer 223 may improve the transparency of the graphene bioelectronic device 200 and the silver nanowire layer 222 may improve the electrical conductivity of the graphene composite layer 220 Can be improved. The graphene multiple layer 220 may be electrically connected to external wiring for power supply and data transmission / reception.

The second protective layer 212 may be disposed on the graphene composite layer 220 to protect and support the graphene composite layer 220. The second passivation layer 211 may be formed of a transparent material such as epoxy. The second passivation layer 212 may expose the upper surface of the graphene composite layer 220 corresponding to the active position.

The metal doping layer 231 is disposed on the graphene composite layer 220 exposed by the second passivation layer 212. The metal doping layer 231 may be, for example, a gold doping layer.

A metal oxide layer 232 is disposed over the metal doped layer 231. The metal oxide layer 232 can be easily formed on the graphene composite layer 220 by the metal doping layer 231. The metal oxide layer 232 may be, for example, an iridium oxide layer.

The tumor sensor 201, the ablation electrode 202, the contact sensor 203 and the viability sensor 205 are connected to each other by a graphene layer 220, a metal doping layer 231 and a metal oxide layer (Not shown). The temperature sensor 204 may comprise only a second graphene layer disposed in the active position. The silver nanowire layer 222 and the first graphene layer 221 under the second graphene layer 223 in the active position in which the temperature sensor 204 is disposed to improve the sensitivity of the temperature monitoring of the temperature sensor 204 Can be removed. The temperature can be monitored by measuring the resistance change of the temperature sensor 204 and the second graphene layer 223 configuring the temperature sensor 204 to increase the resistance of the temperature sensor 204 can be patterned have. The upper surface of the temperature sensor 204 is covered with the second protective layer 212 without being exposed and does not include the metal doping layer 231 and the metal oxide layer 232.

4 to 10 illustrate a method of manufacturing a graphene bioelectronic device according to embodiments of the present invention.

Referring to FIG. 4, a first sacrificial layer 260 is formed on a base substrate 250. For example, the base substrate 250 may be a silicon substrate, and the first sacrificial layer 260 may be formed of nickel using a thermal deposition process.

A first passivation layer 211 is formed on the first sacrificial layer 260. The first passivation layer 211 may be formed by forming a layer on the first sacrificial layer 260 with a transparent material such as epoxy and then patterning the layer.

A graphene layer 221a is formed on the first protective layer 211. The graphene layer 221a may be formed on the copper foil using a chemical vapor deposition process and then transferred onto the first protective layer 211. [

A nanowire layer 222a is formed on the graphene layer 221a. The silver nanowire layer 222a may be formed by spin coating a silver nanowire solution on the graphene layer 221a and then annealing.

Referring to FIG. 5, a photolithography process is performed to pattern the graphene layer 221a and the nanowire layer 222a, and the first graphene layer 221 and the silver nanowire layer 222 are formed. At this time, the silver nanowire layer 222a and the graphene layer 221a in the active position of the temperature sensor can be selectively removed.

Referring to FIG. 6, a graphene layer (not shown) is transferred onto the nanowire layer 222 and then patterned to form a second graphene layer 223. Thereby, the graphene composite layer 220 including the first graphene layer 221, the silver nanowire layer 222, and the second graphene layer 223 is formed. At this time, the second graphene layer 223 in the active position of the temperature sensor may be patterned to increase the resistance of the temperature sensor.

Referring to FIG. 7, a second passivation layer 212 is formed on the graphene composite layer 220. The second passivation layer 212 may be formed by forming a layer on the graphene composite layer 220 with a transparent material such as epoxy and then patterning the layer. The second passivation layer 212 exposes the upper surface of the graphene composite layer 220 corresponding to the active position where the ablation electrode is formed with the other sensor except the temperature sensor.

Referring to FIG. 8, a second sacrificial layer 270 is formed on the second protective layer 212. The second sacrificial layer 270 may be formed of PMMA (poly (methyl methacrylate)). A stamp 280 is disposed on the second sacrificial layer 270. The stamp 280 may be a PDMS (Polydimethylsiloxane) stamp.

Referring to FIG. 9, the first sacrificial layer 260 is removed by performing a wet etching process so that the base substrate 250 is separated from the first protective layer 211. The first passivation layer 211, the graphene composite layer 220 and the second passivation layer 212 are picked up by the stamp 280 and transferred onto the support layer 240. The support layer 240 may be formed of a transparent material such as PDMS.

Referring to FIG. 10, the wet etching process is performed to remove the second sacrificial layer 270, and the stamp 280 is separated from the second protective layer 212. The metal complex layer 220 is contained in the metal chloride solution and the metal doping layer 231 is formed on the upper surface of the graphene composite layer 220 exposed by the second protective layer 212. For example, the metal chloride solution may include gold trichloride, and the metal doping layer 231 may be a gold doping layer.

A metal oxide layer 232 is formed on the metal doped layer 231. The metal oxide layer 232 may be formed of a metal oxide solution using an electroplating process. For example, the metal oxide may be iridium oxide (IrOx). The metal oxide layer 232 may be uniformly formed by the metal doping layer 231. [

Thereby, the graphene bioelectronic device 200 including the graphene composite layer 220 is formed. The graphene bioelectronic device 200 can be supported by the support layer 240 and attached to an endoscope (see 100 in FIG. 1).

11 schematically shows a flow chart of a manufacturing process of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to FIG. 11, a nickel sacrifice layer (100 nm) is formed on a silicon substrate by thermal evaporation. An epoxy layer is formed on the nickel sacrificial layer and patterned to form a bottom epoxy. The bottom graphene is formed on the copper foil through a chemical vapor deposition process, and then the copper foil is removed by wet etching and transferred to the silicon substrate by PMMA. The silver nanowire layer (Ag NW) is formed by spin coating a nanowire solution (0.5 wt%) at 2000 rpm and annealing for 1 minute. The Ag NW / GP layers are patterned by a photolithography process. Silver nanowires in the active position of the temperature sensor are selectively removed to improve temperature monitoring sensitivity. Another GP layer is transferred over the Ag NW / GP layers. The top graphene is patterned and then encapsulated by a top epoxy. The top epoxy layer may be patterned to expose the GP / Ag NW / GP electrode in the active location.

The nickel sacrificial layer is removed by a nickel etchant and the GP / Ag NW / GP electrode is picked up by PMMA and PDMS and then transferred to a thin PDMS layer. GP / AgNW / GP electrode is immersed for 10 minutes in 20mM AuCl 3 solution is a gold-doped layer is formed on the exposed portion of the active site. An iridium oxide layer is formed on the gold-doped layer by electroplating. The uniformity of the iridium oxide layer deposition can be improved by the gold doping layer.

The iridium oxide solution for electroplating can be prepared by stirring and dissolving 150 mg of iridium tetrachloride in 100 mL of ultra-high purity distilled water for 20 minutes. Add 1 mL aliquot of 30% H 2 O 2 aqueous solution and stir for 10 minutes. Then 500 mg of oxalic acid dihydrate is added and stirred for another 10 minutes. Finally, the pH of the solution is adjusted to 10.5 using anhydrous potassium carbonate. The solution is stored at room temperature for one week to stabilize the iridium ions, and a solution having a light purple color is formed. Electrodeposition is performed by a three-electrode method using an electrochemical analyzer. Chronopotentiometry is performed at 0.7 V across the Ag / AgCl reference electrode, graphene hybrid working electrode and platinum counter electrode in an iridium oxide solution for 5 minutes.

Iridium oxide layers electrodeposited on graphene have low interface impedances, minimum volume swell, and high pH sensitivity. Thus, the iridium oxide layer is suitable for sensing small electrical signals, measuring ablation energy transfer, measuring pH changes, and injecting charges into tissues.

12 illustrates the effect of gold doping in the fabrication process of a graphene bioelectronic device according to an embodiment of the present invention. In FIG. 12, the left-aligned drawing shows a case where gold doping is not performed, and the right-aligned drawing shows a case where gold doping is performed.

Referring to FIG. 12, gold doping of the GP / Ag Nw / GP structure reduces the water contact angle and improves surface wetting in an aqueous solution comprising an iridium oxide precursor. This results in a uniform coating of the iridium oxide as shown in the figure. Also, the low impedance properties formed by iridium oxide deposition improve the signal-to-noise ratio and the charge injection efficiency of the graphene bioelectronic device.

[Therapeutic Diagnosis Nanoparticles]

Figure 13 schematically illustrates the therapeutic diagnostic nanoparticles according to embodiments of the present invention.

13, the therapeutic diagnosis nanoparticle 300 includes a metal nanorod 310, a porous shell 320, a PDT (photodynamic) dye 321, a fluorescent dye 322, a chemical 323, , A polymer capsule layer 330, and an antibody 331. [

The metal nanorods 310 may be formed of a material that can be activated by irradiation with a near-infrared laser, for example, gold, and may induce photothermal (PTT) treatment by irradiation with a near-infrared laser.

The porous shell 320 may form a core-shell structure with the metal nanorods 310 and surround the metal nanorods 310. The porous shell 320 may be formed of a material capable of reacting with and growing on the surface of the metal nanorod 310, for example, porous silica. The PDT (Photodynamic) dye 321, the fluorescent dye 322, and the chemical agent 323 may be loaded into the porous shell 320. The PDT dye 321 may include, for example, chlorin e6 (Ce6) and may generate reactive oxygen species (ROS) by irradiation with a red laser. The viability of cancer cells is decreased by the active oxygen species. The fluorescent dye 322 may comprise, for example, rhodamine B, and may be capable of realizing fluorescent images of cancer cells. The chemical agent 323 may comprise, for example, doxorubicin, and the release dose may be controlled by the polymeric capsule layer 330.

The polymer capsule layer 330 may surround the core-shell structure of the metallic nanorod 310 and the porous shell 320. The polymer capsule layer 330 may be formed of a thermosensitive polymer capable of being polymerized at the surface of the porous shell 320, for example, poly (N-isopropylacrylamide) (PNIPAAm) have. The polymer capsule layer 330 has a thermal property for volume change. For example, if the polymer capsule layer 330 does not receive heat, it maintains its volume so as not to discharge the chemicals 323 loaded inside the therapeutic diagnostic nanoparticles 300, but when heated, Thereby releasing the chemical agent 323 to the outside. Accordingly, when the therapeutic diagnosis nanoparticles 300 reach the target position such as a cancer cell in the living body and then receive heat, the volume of the polymer capsule layer 330 decreases to release the chemical drug 323 loaded therein to the target position . Thus, cancer cells and the like can be effectively removed. To prevent accidental release of the chemical agent 323 to other organs other than the target location, the critical temperature for the thermal change to the volume change of the polymer capsule layer 330 is preferably higher than the body temperature (36.5 DEG C).

The antibody 331 is bonded to the surface of the polymer capsule layer 330. Antibody 331 may have binding specificity with an antigen such as cancer cells, for example, cetuximab. Cetuximab binds to the epithelial cell proliferation factor receptor on the cell surface and blocks the pathway for promoting cell division, thereby preventing the proliferation of cancer cells. For example, the cetuximab allows active targeting of the epidermal growth factor receptor overexpressed in colorectal cancer (HT-29) cells. That is, the therapeutic diagnosis nanoparticles 300 can be actively targeted by the antibody 331.

14 shows the structure and manufacturing process of the therapeutic diagnostic nanoparticles according to an embodiment of the present invention.

14, the therapeutic diagnostic nanoparticles may be fabricated using a variety of techniques including gold nanorods, AuNR, a mesoporous silica shell (MSS), poly (N-isopropylacrylamide) PNIPAAm) capsule layer, Chlorin e6, Rhodamin B, Doxorubicin, and Cetuximab.

The therapeutic diagnostic nanoparticles can be formed by several step reactions and separation processes. The formation process can be accomplished by the following steps: i) synthesis of a gold nanorod, ii) synthesis of a porous silica shell, iii) loading of a PDT dye and a fluorescent dye, iv) formation of a PNIPAAm capsule layer, and v) And loading of doxorubicin.

I) Synthesis of gold nanorods: Au seed solution was prepared by adding NaBH 4 solution (600 μL, 10 mM) with HAuCl 4 H 2 O (250 μL, 10 mM) and cetyltrimethylammonium bromide (CTAB) ) ≪ / RTI > The growth solution was prepared by adding HAuCl 4 .3H 2 O (1.7 mL, 10 mM) and AgNO 3 (250 μL, 10 mM) to the CTAB solution (40 mL, 100 mM) and L- ascorbic acid (270 μL, 100 mM) . This gold seed is converted to gold nanorods by addition of seed solution (420 μL) into the growth solution and allowed to react for 3 hours. The final product solution is centrifuged twice.

Ii) Synthesis of porous silica shell: The silica shell grows on the surface of gold nanorods. Tetraethyl orthosilicate (TEOS) (30 μL) is injected into gold nanorod bath solution (50 mL) under alkaline conditions (pH 10-11) and reacted with gold nanorods for 4 hours. Functionalization of the silica surface was carried out by adding 10 μL of (3-aminopropyl) triethoxysilane (10 μL) and 3- (methacryloxy) propyl triethoxysilane (10 μL ), And the solution is stirred for 4 hours. Silica-coated gold nanorods (Au NR @ MSS) are centrifuged twice and diffuse in ethanol. To form pores in the silica shell, HCl is added to the nanoparticle-ethanol suspension to regulate the pH to 1-2 and refluxed to remove the CTAB template. The resulting silica-coated gold nanorods (Au NR @ MSS) are centrifuged twice and diffused into water.

Iii) Loading of PDT dye and Fluorescent (FL) dye: Chlorine e6 (Ce6) was synthesized from N- (3-dimethylaminopropyl) -N'- ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide NHS). And functionalized chlorine e6 reacts with silica coated gold nanorods (Au NR @ MSS) for 12 hours. To load the fluorescent (FL) dye, rhodamine B isothiocyanate is mixed and reacted for 12 hours. After bonding, the silica-coated gold nanorods (Au NR @ MSS) are centrifuged and diffused into water.

Iv) Formation of PNIPAAm Capsule Layer: To form the PNIPAAm capsule layer, a silica coated gold nanorod (Au NR @ MSS) solution (5 mL) was mixed with N-isopropylacrylamide (NIPAAm) (12 mL, 100 mM) (20 mL), sodium dodecyl sulfate (200 μL), and the mixture was stirred at room temperature for 1 hour. The solution is heated to 70 < 0 > C to remove oxygen and bubbled with argon. After 30 minutes, potassium persulfate (1 mL, 20 mM) was injected to begin the polymerization. The Au NR @ MSS @ PNIPAAm solution is centrifuged twice to remove unreacted chemical components.

V) Loading of antibody binding and doxorubicin (Dox): Cetuximab (antibody) (2 mL, 5 mg / mL) is added to the AuNR @ MSS @ PNIPAAm solution for binding. The NHS terminal group reacts with the PEG terminal group. This antibody bound AuNR @ MSS @ PNIPAAm is centrifuged and diffused in PBS. Then add doxorubicin (Dox) (1 mL, 0.6 mg / mL) solution to the nanoparticle solution (5 mL) and stir for one day. Excess doxorubicin (Dox) can be removed by centrifuging the nanoparticles.

Figure 15 shows the in vivo toxicity test results of the therapeutic diagnostic nanoparticles according to one embodiment of the present invention.

15, when tissue images were analyzed in various organs of mice and normal mice injected with therapeutic diagnostic nanoparticles, the therapeutic diagnostic nanoparticles did not cause any inflammation in the respective organs, and the therapeutic diagnostic nanoparticles Is not toxic.

Outline structure and image of endoscopic system

FIG. 16 shows a schematic structure and corresponding image of an endoscope system according to an embodiment of the present invention, FIG. 17 shows the integration process of a graphene bioelectronic device on an endoscope, FIG. 18 shows a graphene bioelectronic Indicates the external connection of the device.

16 to 18, when cancer cells are detected and confirmed, a large part of the cancer cell tissue is excised through forceps, and then high frequency ablation using graphene bioelectronic device is performed. Feedback modulations of this ablation therapy are based on continuous monitoring of temperature, contact, and cell / tissue viability. Photodynamic (PDT) therapy, phototherapy (PTT) treatment induced by PDT dye (chlorin e6; Ce6), gold nanorod (Au NR), and chemical drugs (doxorubicin, Dox) loaded on porous silica cells (MSS) , And chemotherapy can be activated through an irradiated red or near-infrared laser to effectively remove residual cancer cells around the treatment site. A thermosensitive poly (N-isopropylacrylamide) (PNIPAAm) capsule layer prevents doxorubicin (Dox) from being released without irradiation of the near infrared ray laser. Prior to proceeding with the treatment and diagnosis process, the graphene bioelectronic device is cleaned, sterilized and adhered to the endoscope (Fig. 17a, b). The graphene bioelectronic device can be mechanically, mechanically, mechanically, mechanically, mechanically, or mechanically, without generating cracks during installation, removal, and routing, due to the flexible nature of graphene, ultra thin structure, and high mechanical deformation achieved by neutral mechanical plane designs. And may be bent or bent.

Grapina  Characteristics of bioelectronic devices

Figure 19 illustrates the transparency and detail design of a graphene bioelectronic device in accordance with an embodiment of the present invention.

19A shows the transparency in the four dotted line regions (i, ii, iii, iv) of the graphene bioelectronic device, FIG. 19 compares the transparency of the graphene bioelectronic device and the gold-based electronic device, 19D shows an image of a graphen bioelectronic device corresponding to FIG. 19C, and FIG. 19E shows an image of a gold-based electronic device corresponding to FIG. 19C . 19C to FIG. 19E, the right drawing is an enlarged view of the four dotted line areas (i, ii, iii, iv) in the left drawing. Referring to FIG. 19, the graphene bioelectronic device exhibits uniformity and high transparency (total transmittance of 80%) in all four dotted lines and exhibits a very high transparency compared to gold-based electronic devices.

Figure 20 shows the thermal stability of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to FIG. 20, the graphene bioelectronic device shows a similar impedance compared to that before sterilization treatment even after sterilization treatment using hot saturated steam at a sterilization processor (120 ° C, 200 kPa, 15 min). Therefore, it can be seen that the graphene bioelectronic device has excellent thermal stability.

Figure 21 shows the mechanical stability of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to FIG. 21, there is little change in resistance of the graphene bioelectronic device after bending and bit deflection at various curvature radii. The ultra thin structure of the graphene bioelectronic device allows for better mechanical deformation capability. Thus, it can be seen that the graphene bioelectronic device has excellent mechanical stability.

22 illustrates material properties of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to Figure 22, the graphene configuration of the graphene bioelectronic device is characterized by Raman spectroscopy. The graphene configuration consists of 2-3 graphene layers based on the relative peak intensities (I 2D / G = 1.01) of 2D and G bands. The defect-related D band peak is strongly suppressed, and high-quality graphene synthesis is exhibited. Silver nanowires are analyzed by X-ray diffraction (XRD). The detection of the peak of silver (Ag 2 O) (θ = 32 °) represents a small amount of silver oxide formed at the surface during thermal annealing. Additional oxidation is minimized by passivation with top graphene. Electrodeposited Iridium oxide film is characterized by a X-ray photoelectron spectroscopy (XPS) indicates the bond between iridium and oxygen atoms, and iridium 62.1 4f 7/2 and iridium 4f 5/2 peak energy of 65.0eV. Compared to the characteristic XPS peaks of metallic iridium (61.1 and 64.1 eV) and the iridium oxide standard (62.7 and 65.7 eV), electrodeposited iridium oxide is present in a highly oxidized form.

23 shows the electrical stability of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to Figure 23, in order to be suitable as a sensor and an actuator in the course of endoscopic use, the material of the electronic device must withstand temperature changes during high-frequency ablation and exposure to multiple electrochemical cycles in a biofluidic environment. The graphene bioelectronic maintains a stable impedance value in the temperature range of 20-50 ° C in PBS. The resistance change of interconnection is small. The graphene bioelectronic device maintains electrochemical stability even after multiple cyclic voltammetric tests in PBS. Stability of impedance in fetal calf serum (Life technologies, 16000) is confirmed over 6 hours and shows stable electrochemical activity in biofluidic environment. No new material is formed during oxidation and reduction.

tumor Sensing

FIG. 24 shows tumor sensing characteristics of a graphene bioelectronic device according to an embodiment of the present invention, and FIG. 25 shows a pH sensing characteristic of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to FIGS. 24 and 25, the tumor sensor can distinguish cancer tissues from normal tissues according to impedance differences. Cancer tissue exhibits significantly lower impedance compared to healthy tissue. This difference in impedance can be used to detect tumor tissue and tumor growth. Bio-impedence recordings are highly dependent on size, spacing, and density, which can change electrical signals and charge storage in tissue. Specific frequency ranges are also important for tissue differentiation based on bio-impedance analysis. Impedance-based tumor detection can also be used to diagnose breast, esophageal, prostate, and brain tumors. The endoscopic sensing provided in the present invention represents an in-vivo analysis of a subcutaneous colon cancer (HT-29) model of a mouse (BALB / c-nude mouse). The biosensor measures the impedance difference between cancer tissue and normal skin tissue. In both in vitro and in vivo experiments, colon cancer (HT-29) tissue exhibits lower impedance than normal tissue.

Tumor sensors can detect cancer tissues by measuring changes in pH levels around cancer tissues. Changes in the pH level around the tumor caused by the rapid metabolism of cancer function as an important marker for tumor detection. The extracellular pH level in cancer tissues is lower than the pH in normal tissues due to increased lactate production and reduced intercellular fluid buffering. Since the surface zeta potential of the graphene multiple layer has pH dependency, the pH can be sensed by measuring the open circuit potential. The measured open circuit potential value is converted to a pH value based on the calibration curve. The pH sensor according to embodiments of the present invention measures the pH level near the tumor to distinguish between tumor tissue and normal tissue. Conventional pH sensors use a 3-electrode method for pH measurement in solution. However, the pH sensor according to embodiments of the present invention is based on a two-electrode. That is, the pH sensor is composed of the working electrode of the graphene composite layer portion where the iridium oxide is electrodeposited and the counter electrode of the gold doped graphene composite layer portion. This is because the electrodeposited iridium oxide has pH-sensitive properties. The pH sensor can be reproduced during the pH change of the buffer solution, and the pH value of cancer tissue and normal tissue can be measured in vivo.

High frequency Ablation  And feedback monitoring

FIG. 26 shows high frequency ablation characteristics of a graphene bioelectronic device according to an embodiment of the present invention, FIG. 27 shows touch sensing and temperature sensing characteristics of a graphene bioelectronic device according to an embodiment of the present invention, 28 shows the cell viability sensing characteristic of a graphene bioelectronic device according to an embodiment of the present invention.

Referring to Figures 26 to 28, high frequency ablation can be performed by connecting an ablation electrode to a radio frequency generator. The on and off contacts are monitored through the impedance change of the touch sensor. The temperature during high-frequency ablation is monitored continuously by measuring the resistance change of the temperature sensor by a digital multimeter, and is confirmed by the IR camera. The tissue viability can be measured by impedance changes before and after high-frequency ablation. As such, the conformal contact and temperature are continuously monitored during the ablation. The viability sensor distinguishes the ablated tissue from the non-ablated tissue by measuring the local impedance change.

Therapeutic diagnosis using nanoparticles Targeting , Imaging , And treatment

Figure 29 shows the targeting, imaging, and therapeutic properties of therapeutic diagnostic nanoparticles in accordance with one embodiment of the present invention.

Referring to FIG. 29, therapeutic diagnostic nanoparticles used in combination with graphene bioelectronic devices provide additional cancer diagnosis and targeted therapeutic methods. The cell TEM image of Figure 29b shows the targeted absorption of the nanoparticles by cancer cells, which is evidenced by the fluorescence image in Figure 29c and the flow cell analysis data in Figure 29d. The therapeutic diagnostic nanoparticles fight cancer cells through the generation of reactive oxygen species (ROS), mineral oil exotherm, and controlled drug release. The photoactivation of the therapeutic diagnostic nanoparticles is limited to the laser irradiation site and is controlled by controlling the intensity of the laser. The direct control of the laser light transmitted through the endoscope solves many problems associated with the transmission depth of light. As shown in the results of the flow cytometry, the PDT dye on the therapeutic diagnostic nanoparticles is more effectively transmitted to and absorbed by the cancer cells as compared with the control group. When irradiated by a red laser (wavelength 670 nm), the PDT dye generates active oxygen species and cell viability is reduced. The temperature is optimized photothermically by varying particle concentration, near infrared laser intensity (808 nm), and irradiation time, and is optimized to reduce cancer cell viability. Increasing the temperature changes the hydrodynamic diameter of the therapeutic diagnostic nanoparticles from about 290 nm to about 110 nm by shrinking the PNIPAAm capsule layer, which leads to the release of doxorubicin (Dox) loaded into the therapeutic diagnostic nanoparticles . The release temperature is preferably designed to be higher than body temperature. PNIPAAm block copolymers inhibit drug release without laser irradiation and minimize the side effects of doxorubicin (Dox). The viability test of cancer cells after combined treatment of PDT treatment, PTT treatment, and chemotherapy (using GaAs pulsed laser, wavelength 690 nm, red laser of power 30 mW, wavelength 808 nm, power 30 mW near infrared ray laser) .

Colon cancer treatment using endoscopic system

30 schematically shows a tumor treatment process using an endoscopic system according to an embodiment of the present invention.

Referring to FIG. 30, a typical medical application example of an endoscopic system includes colorectal cancer treatment. The treatment begins by injecting therapeutic diagnostic nanoparticles into the vein, and a specific antibody (cetuximab) bound onto the surface of the therapeutic diagnostic nanoparticles targets colon cancer cells (HT-29). Imaging of fluorescent dyes loaded in the therapeutic diagnostic nanoparticles provides visual information about the spatial distribution of cancer cells. The endoscope allows laser light to approach the suspected location exposed to the therapeutic diagnostic nanoparticles. These sites can be easily observed in graphene bioelectronics with a total transmittance of 80% in the visible range. Graphene bioelectronics and their associated sensors provide additional electrochemical analysis of tumor distribution.

31 is a view for explaining in vivo colorectal cancer treatment using an endoscope system according to an embodiment of the present invention.

31, a transparent graphene bioelectronic device mounted on an endoscope and a therapeutic diagnostic nanoparticle activated by an induction laser can be applied as an in vivo model. Endoscopic treatment of colon cancer (HT-29) grown on the subcutaneous surface of mice begins by injecting the therapeutic diagnostic nanoparticles intravenously via the tail vein. The colon cancer model is difficult to use in large animals, and because of the large size of endoscopes in view of the gastrointestinal tract of small animals, the research is carried out using a subcutaneous colon cancer model. Since the release of doxorubicin loaded onto the therapeutic diagnostic nanoparticles is inhibited by PNIPAAm encapsulation, side effects from doxorubicin (Dox) are minimized. Fluorescent images of the organs preserved and biological distribution analysis data show successful targeting. A large number of therapeutic diagnostic nanoparticles accumulate in the tumor within 6 hours of injection. Most therapeutic diagnostic nanoparticles are removed from the blood in a day because of their short circulation time.

Fluorescence optical images of nanoparticle-targeted tumors can be obtained in the body 6 hours after injection of therapeutic diagnostic nanoparticles, and suspected tumor sites and tumor-free sites can be identified. The details can be visually observed through the camera installed in the endoscope. The image of the tumor-grown surface captured by the endoscopic camera indicates that the transparent graphene bioelectronic device does not interfere with visual observation, whereas the metal-based electronic device causes severe disturbance. Once the cancerous cells are identified, the tumor is removed using high frequency ablation therapy. In this case, the contact sensor is used to sense the conformal contact between the graphene bioelectronic device and the tissue. In contact mode during high frequency ablation, visual observation of the tumor is not possible. Impedance-based tumor sensors are therefore used to locate cancerous tissues according to the low impedance and pH levels of tumor cells. Monitoring of temperature changes provides additional guidance during high-frequency ablation. Finally, tissue viability is measured to confirm ablation therapy.

Together with physical treatment through graphene bioelectronics, cancer cells are treated with therapeutic diagnostic nanoparticles. These therapeutic diagnostic nanoparticles are locally activated using red and near-infrared lasers to induce PDT therapy, PTT therapy, and chemotherapy. The effect of these multiple interventions is confirmed in vivo by tracking changes in tumor volume (HT-29) based on visual observation. In the control group (no treatment), the tumor volume increases after 2 weeks, but the treated group decreases the tumor volume. Combined therapies (PDT, PTT, and chemotherapy) do not lead to a dramatic reduction in tumor volume, although tumor growth in rats does not decrease the volume of the tumor when irradiated with laser without nanoparticle injection or treated with chemotherapy alone without nanoparticles It looked. After treatment, the H & E (hematoxylin and eosin) staining image of the tumor shows an irregular structure due to the cell apoptosis of cancer cells. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis shows apoptosis of cancer cells after combined treatment.

Hereinafter, specific embodiments of the present invention have been described. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

10: endoscope system 100: endoscope
110: laser supplier 120: camera
130: Saline supply 200: Graphene bioelectronic device
201: tumor sensor 202: ablation electrode
203: contact sensor 204: temperature sensor
205: Survival force sensor 211: First protective layer
212: second protective layer 220: graphene composite layer
211: first graphene layer 212: silver nanowire layer
213: second graphene layer 231: metal doped layer
232: metal oxide layer 240: support layer

Claims (15)

A graphene bioelectronic device comprising a graphene composite layer comprising at least two graphene layers. The method according to claim 1,
Wherein the graphene composite layer comprises:
The first graphene layer,
A silver nanowire layer disposed over the first graphene layer, and
Wherein the silver comprises a second graphene layer disposed over the nanowire layer. 3. The method of claim 2,
And a plurality of metal oxide layers disposed on the second graphene layer and spaced apart from the second graphene layer. The method of claim 3,
Wherein the metal oxide layer comprises an iridium oxide layer. The method of claim 3,
And a metal doping layer disposed between the second graphene layer and the metal oxide layer. 6. The method of claim 5,
Wherein the metal doping layer comprises a gold doping layer. The method of claim 3,
And a sensor and an ablation electrode formed by the graphene composite layer and the metal oxide layer. 8. The method of claim 7,
Wherein the sensor further comprises at least one of a tumor sensor, a touch sensor, and a viability sensor. 9. The method of claim 8,
Wherein the tumor sensor includes a working electrode and a counter electrode,
Wherein the working electrode comprises the graphene composite layer and the metal oxide layer,
Wherein the counter electrode comprises the graphene composite layer and does not include the metal oxide layer. 9. The method of claim 8,
Further comprising a temperature sensor comprising only a patterned portion of the second graphene layer. ≪ RTI ID = 0.0 > 8. < / RTI > The method according to claim 1,
Wherein the graphene bioelectronic device is attached and used on a camera of an endoscope. A first protective layer;
A first graphene layer disposed over the first passivation layer;
A silver nanowire layer disposed over the first graphene layer;
A second graphene layer disposed over the silver nanowire layer; And
And a second protective layer disposed over the second graphene layer. 13. The method of claim 12,
Wherein the first protective layer and the second protective layer are formed of transparent epoxy. 13. The method of claim 12,
Further comprising a metal oxide layer disposed over the second graphene layer,
Wherein the second protective layer exposes at least a portion of the second graphene layer,
Wherein the metal oxide layer is disposed on an exposed portion of the second graphene layer. 15. The method of claim 14,
And a metal doping layer disposed between the second graphene layer and the metal oxide layer.


KR1020150080349A 2015-06-08 2015-06-08 Graphene bioelectronic device KR101789711B1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR1020150080349A KR101789711B1 (en) 2015-06-08 2015-06-08 Graphene bioelectronic device
PCT/KR2016/005950 WO2016200105A2 (en) 2015-06-08 2016-06-03 Graphene bioelectronic device, treatment and diagnosis nanoparticle, and endoscope system

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020150080349A KR101789711B1 (en) 2015-06-08 2015-06-08 Graphene bioelectronic device

Publications (2)

Publication Number Publication Date
KR20160144069A true KR20160144069A (en) 2016-12-16
KR101789711B1 KR101789711B1 (en) 2017-10-25

Family

ID=57735721

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020150080349A KR101789711B1 (en) 2015-06-08 2015-06-08 Graphene bioelectronic device

Country Status (1)

Country Link
KR (1) KR101789711B1 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108969883A (en) * 2017-05-31 2018-12-11 李宇光 The production method and application of graphene bioelectricity sports chip
WO2019083294A1 (en) * 2017-10-27 2019-05-02 서울대학교산학협력단 Core-shell nanowire, method for forming core-shell nanowire, and stretchable composite comprising core-shell nanowire
KR20200019648A (en) * 2020-02-10 2020-02-24 서울대학교산학협력단 Core-shell nanowire, method of forming the core-shell nanowire, and stretchable composites comprising the core-shell nanowire
KR20200031579A (en) * 2020-02-10 2020-03-24 서울대학교산학협력단 Core-shell nanowire, method of forming the core-shell nanowire, and stretchable composites comprising the core-shell nanowire
CN113607646A (en) * 2021-08-03 2021-11-05 江苏省特种设备安全监督检验研究院 SERS substrate and preparation method thereof
WO2022203118A1 (en) * 2021-03-26 2022-09-29 연세대학교 산학협력단 Multi-channel array element using graphene composite electrode for brain insertion
KR20220134404A (en) * 2021-03-26 2022-10-05 연세대학교 산학협력단 Muti Channel Array Element Using Hybrid Graphene Electrode Brain Inserted

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101159012B1 (en) * 2010-11-18 2012-06-21 경희대학교 산학협력단 Electrode for electrochemical biosensor and biosensor including the same

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108969883A (en) * 2017-05-31 2018-12-11 李宇光 The production method and application of graphene bioelectricity sports chip
CN108969883B (en) * 2017-05-31 2021-12-28 李宇光 Manufacturing method and application of graphene bioelectricity health chip
WO2019083294A1 (en) * 2017-10-27 2019-05-02 서울대학교산학협력단 Core-shell nanowire, method for forming core-shell nanowire, and stretchable composite comprising core-shell nanowire
JP2021509433A (en) * 2017-10-27 2021-03-25 ソウル大学校産学協力団Ｓｅｏｕｌ Ｎａｔｉｏｎａｌ Ｕｎｉｖｅｒｓｉｔｙ Ｒ＆Ｄｂ Ｆｏｕｎｄａｔｉｏｎ Elastic composites containing core-shell nanowires, the method for forming core-shell nanowires, and the core-shell nanowires.
US11419534B2 (en) 2017-10-27 2022-08-23 Seoul National University R&Db Foundation Core-shell nanowire, method of forming core-shell nanowire, and stretchable composite comprising core-shell nanowire
KR20200019648A (en) * 2020-02-10 2020-02-24 서울대학교산학협력단 Core-shell nanowire, method of forming the core-shell nanowire, and stretchable composites comprising the core-shell nanowire
KR20200031579A (en) * 2020-02-10 2020-03-24 서울대학교산학협력단 Core-shell nanowire, method of forming the core-shell nanowire, and stretchable composites comprising the core-shell nanowire
WO2022203118A1 (en) * 2021-03-26 2022-09-29 연세대학교 산학협력단 Multi-channel array element using graphene composite electrode for brain insertion
KR20220134404A (en) * 2021-03-26 2022-10-05 연세대학교 산학협력단 Muti Channel Array Element Using Hybrid Graphene Electrode Brain Inserted
CN113607646A (en) * 2021-08-03 2021-11-05 江苏省特种设备安全监督检验研究院 SERS substrate and preparation method thereof
CN113607646B (en) * 2021-08-03 2023-12-26 江苏省特种设备安全监督检验研究院 SERS substrate and preparation method thereof

Also Published As

Publication number Publication date
KR101789711B1 (en) 2017-10-25

Similar Documents

Publication Publication Date Title
KR101789711B1 (en) Graphene bioelectronic device
Lee et al. An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment
Sundaram et al. Engineering of 2D transition metal carbides and nitrides MXenes for cancer therapeutics and diagnostics
Dai et al. Two-dimensional tantalum carbide (MXenes) composite nanosheets for multiple imaging-guided photothermal tumor ablation
Yang et al. Multifunctional Bi@ PPy-PEG core–shell nanohybrids for dual-modal imaging and photothermal therapy
Xu et al. Black phosphorus nanosheet with high thermal conversion efficiency for photodynamic/photothermal/immunotherapy
Phan et al. Photoacoustic imaging-guided photothermal therapy with tumor-targeting HA-FeOOH@ PPy nanorods
Cui et al. Fluorescent silicon nanorods-based nanotheranostic agents for multimodal imaging-guided photothermal therapy
Guo et al. Intelligent nanoenzyme for T1-weighted MRI guided theranostic applications
Sun et al. Camouflaged gold nanodendrites enable synergistic photodynamic therapy and NIR biowindow II photothermal therapy and multimodal imaging
Qiu et al. Highly sensitive surface-enhanced Raman scattering (SERS) imaging for phenotypic diagnosis and therapeutic evaluation of breast cancer
CN106177950B (en) A kind of gold-covered nano stick, preparation method and application
Liu et al. Surface Plasmonic Enhanced Imaging-Guided Photothermal/Photodynamic Therapy Based on Lanthanide–Metal Nanocomposites under Single 808 nm Laser
Lee et al. Flexible and biodegradable electronic implants for diagnosis and treatment of brain diseases
Qiao et al. A tumor microenvironment-triggered and photothermal-enhanced nanocatalysis multimodal therapy platform for precise cancer therapy
Tran et al. Direct synthesis of rev peptide-conjugated gold nanoparticles and their application in cancer therapeutics
Nguyen et al. Recent progress and challenges of MOF-based nanocomposites in bioimaging, biosensing and biocarriers for drug delivery
CN107432932A (en) Nanometer ruthenium composite and preparation method thereof and the application in carrying medicine and preparing antineoplastic
Bi et al. A H2S-triggered dual-modal second near-infrared/photoacoustic intelligent nanoprobe for highly specific imaging of colorectal cancer
Lee et al. Colloidal porous AuAg alloyed nanoparticles for enhanced photoacoustic imaging
Xu et al. Construction of a polypyrrole-based multifunctional nanocomposite for dual-modal imaging and enhanced synergistic phototherapy against cancer cells
Sun et al. Decitabine-loaded gold nanocages for photothermal cancer therapy via DNA hypermethylation reversal
Darrigues et al. Raman spectroscopy using plasmonic and carbon-based nanoparticles for cancer detection, diagnosis, and treatment guidance. Part 2: Treatment
Li et al. Designing intelligent nanomaterials to achieve highly sensitive diagnoses and multimodality therapy of bladder cancer
Geng et al. Hypoxia-Responsive Aggregation of Gold Nanoparticles for Near-Infrared-II Photoacoustic Imaging-Guided Enhanced Radiotherapy

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
E902 Notification of reason for refusal
E701 Decision to grant or registration of patent right
GRNT Written decision to grant