KR20130104820A - Memory capacitor device including aptamer coated au nanoparticle layer and preparation method thereof - Google Patents
Memory capacitor device including aptamer coated au nanoparticle layer and preparation method thereof Download PDFInfo
- Publication number
- KR20130104820A KR20130104820A KR1020120026697A KR20120026697A KR20130104820A KR 20130104820 A KR20130104820 A KR 20130104820A KR 1020120026697 A KR1020120026697 A KR 1020120026697A KR 20120026697 A KR20120026697 A KR 20120026697A KR 20130104820 A KR20130104820 A KR 20130104820A
- Authority
- KR
- South Korea
- Prior art keywords
- substrate
- aptamer
- capacitor device
- memory capacitor
- manufacturing
- Prior art date
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 43
- 108091023037 Aptamer Proteins 0.000 title claims abstract description 39
- 239000003990 capacitor Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title 1
- 239000000758 substrate Substances 0.000 claims abstract description 33
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000003277 amino group Chemical group 0.000 claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 claims abstract description 20
- 238000003860 storage Methods 0.000 claims abstract description 20
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims abstract description 19
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims abstract description 19
- 239000004065 semiconductor Substances 0.000 claims abstract description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052814 silicon oxide Inorganic materials 0.000 claims abstract description 10
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims abstract description 7
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229940014800 succinic anhydride Drugs 0.000 claims abstract description 7
- 239000010931 gold Substances 0.000 claims description 41
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 39
- 229910052737 gold Inorganic materials 0.000 claims description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims description 12
- -1 silane compound Chemical class 0.000 claims description 8
- 229910000077 silane Inorganic materials 0.000 claims description 7
- 239000000427 antigen Substances 0.000 claims description 6
- 108091007433 antigens Proteins 0.000 claims description 6
- 102000036639 antigens Human genes 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 6
- 238000000576 coating method Methods 0.000 claims description 6
- 239000013077 target material Substances 0.000 claims description 6
- 108010052285 Membrane Proteins Proteins 0.000 claims description 5
- 102000018697 Membrane Proteins Human genes 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- SLIUAWYAILUBJU-UHFFFAOYSA-N pentacene Chemical compound C1=CC=CC2=CC3=CC4=CC5=CC=CC=C5C=C4C=C3C=C21 SLIUAWYAILUBJU-UHFFFAOYSA-N 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229920001609 Poly(3,4-ethylenedioxythiophene) Polymers 0.000 claims description 2
- 230000027455 binding Effects 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims 2
- 239000012460 protein solution Substances 0.000 claims 1
- 229960002317 succinimide Drugs 0.000 claims 1
- 150000004756 silanes Chemical class 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 238000003618 dip coating Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000005669 field effect Effects 0.000 description 1
- XPJRQAIZZQMSCM-UHFFFAOYSA-N heptaethylene glycol Polymers OCCOCCOCCOCCOCCOCCOCCO XPJRQAIZZQMSCM-UHFFFAOYSA-N 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 238000002207 thermal evaporation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K10/00—Organic devices specially adapted for rectifying, amplifying, oscillating or switching; Organic capacitors or resistors having potential barriers
-
- 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
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Semiconductor Memories (AREA)
Abstract
Description
본 발명은 금 나노입자 층을 포함하는 유기 메모리 캐패시터 소자 및 이의 제조방법에 관한 것으로서, 더욱 상세하게는 압타머 코팅된 금 나노입자 층을 포함하는 유기 메모리 캐패시터 소자 및 이의 제조방법에 관한 것이다.
The present invention relates to an organic memory capacitor device comprising a gold nanoparticle layer and a method of manufacturing the same, and more particularly to an organic memory capacitor device comprising aptamer-coated gold nanoparticle layer and a method of manufacturing the same.
최근 몇 년 동안, 플로팅 게이트(FG)로서 나노입자를 사용하는 유기 메모리 소자에 대한 연구가 집중되고 있다. 현재, 종래의 플래쉬 메모리 셀은 나노규모 금속 산화물 전계 효과 트랜지스터(MOSFET)에 기초하여 제작되고 있다. 최근, 플렉시블 전자 소자에 대한 응용은 유기계 소자에 대한 연구를 필요로 한다. 가요성은 접히고 착용 가능한 전자 소자와 같은 미래 응용 분야에 있어서 특히 중요하다. 지금까지, 펜타센과 같은 유기 반도체는 유기 소자 분야의 반도체 재료로 광범위하게 사용되어 왔다. 유기 플렉시블 메모리 소자는 조립 과정이 간단하고, 저온에서 제조 가능하며, 저 비용으로 제조할 수 있다는 점에서 매우 매력적이다. In recent years, research has focused on organic memory devices using nanoparticles as floating gates (FGs). Currently, conventional flash memory cells are fabricated based on nanoscale metal oxide field effect transistors (MOSFETs). Recently, application to flexible electronic devices requires research on organic devices. Flexibility is particularly important for future applications such as folded and wearable electronic devices. Until now, organic semiconductors such as pentacene have been widely used as semiconductor materials in the field of organic devices. Organic flexible memory devices are very attractive in that the assembly process is simple, can be manufactured at low temperatures, and can be manufactured at low cost.
종래 유기 메모리 소자를 제조하는 방법 중 생체 물질을 이용하는 방법은 구조적인 균일성, 분자 인식 및 자기 조립과 같은 고유의 특성이 있어 전도 유망한 분야이다. 이러한 생체 물질을 이용하는 유기 메모리 캐패시터 소자의 제조방법으로서, 항원항체 반응, DNA 결합 등을 이용하는 방법이 공지되어 있으나, 상기 방법들은 공정이 복잡하다는 단점이 있다. 또한, 항원항체 반응은 특이성이 매우 뛰어나서 정확한 진단용 도구로 매우 가치가 높은 장점이 있으나, 특정 항체의 합성은 고 난이도의 배양과 합성을 요구하며 각 배치에 따라 합성된 항체의 특성이 조금씩 다를 수 있다는 문제점도 내포하고 있고, 고가에서 오는 문제점이 상용화의 최대 걸림돌이 되고 있다. BACKGROUND OF THE INVENTION In the method of manufacturing a conventional organic memory device, a method using a biomaterial is a promising field because of its inherent characteristics such as structural uniformity, molecular recognition, and self-assembly. As a method of manufacturing an organic memory capacitor device using such a biomaterial, a method using an antigen antibody reaction, DNA binding, or the like is known, but these methods have a disadvantage in that the process is complicated. In addition, antigen-antibody reactions are highly specific and therefore highly valuable as a tool for accurate diagnosis. However, the synthesis of specific antibodies requires culture and synthesis of a high degree of difficulty, and the characteristics of the synthesized antibodies may be slightly different for each batch. There are also problems, and problems that come from high prices are the biggest obstacles to commercialization.
본 발명의 목적은 기존의 복잡한 공정 대신 간단한 공정으로 제조될 수 있으며 우수한 소자 재현성과 신뢰성을 가지는 캐패시터 타입의 유기 메모리 캐패시터 소자의 제조방법 및 이에 의해 제조된 유기 메모리 캐패시터 소자를 제공하는 것이다. SUMMARY OF THE INVENTION An object of the present invention is to provide a method of manufacturing a capacitor type organic memory capacitor device which can be manufactured by a simple process instead of a conventional complicated process and has excellent device reproducibility and reliability, and an organic memory capacitor device manufactured thereby.
본 발명의 다른 목적은 압타머와 특이적으로 결합하는 특정 단백질(타겟 물질)이 압타머에 노출되었을 때 나타나는 금 나노입자 층(전하 저장층)의 정전 용량을 측정함으로써 타겟 물질의 검출이 가능한 압타머를 이용한 바이오 센서를 제공하는 것이다.
Another object of the present invention is to detect the target material by measuring the capacitance of the gold nanoparticle layer (charge storage layer) that appears when a specific protein (target material) that specifically binds to the aptamer is exposed to the aptamer. It is to provide a biosensor using a timer.
상기 목적을 달성하기 위해서, 본 발명은 메모리 소자의 전하 저장층을 구성하는 금 나노 입자의 표면에 단백질에 대한 친화력이 높은 DNA 핵심 가닥인 압타머(Aptamer)를 흡착 고정시킴으로써 압타머 코팅된 금 나노 입자층을 구비한 유기 메모리 캐패시터 소자의 제조방법을 제공한다. In order to achieve the above object, the present invention provides aptamer-coated gold nanoparticles by adsorption and fixing aptamer, a DNA core strand having a high affinity for proteins, on the surface of the gold nanoparticles constituting the charge storage layer of the memory device. A method of manufacturing an organic memory capacitor device having a particle layer is provided.
구체적으로, 본 발명은 (S1) 실리콘 산화막이 증착된 기판을 아민기를 갖는 실란 화합물로 처리하여 상기 기판 표면을 아민기로 기능화시키는 단계; (S2) S1 단계에서 아민기로 기능화된 기판 표면을 숙신산 무수물로 처리하고 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드 용액과 N-하이드록시숙신이미드로 코팅하는 단계; (S3) 상기 기판 표면에 PSMA 단백질(전립선 특이적 막 단백질 항원)을 결합시키는 단계; (S4) 상기 PSMA 단백질과 압타머 코팅된 금 나노입자를 결합시켜 전하 저장층을 형성하는 단계; 및 (S5) 유기 반도체 층 및 전극을 형성하는 단계를 포함하는 유기 메모리 캐패시터 소자의 제조방법을 제공한다. Specifically, the present invention comprises the step of treating the substrate on which the (S1) silicon oxide film is deposited with a silane compound having an amine group to functionalize the surface of the substrate with an amine group; (S2) treating the surface of the substrate functionalized with an amine group in step S1 with succinic anhydride and coating with 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution and N-hydroxysuccinimide; (S3) binding a PSMA protein (prostate specific membrane protein antigen) to the substrate surface; (S4) combining the PSMA protein with the aptamer coated gold nanoparticles to form a charge storage layer; And (S5) forming an organic semiconductor layer and an electrode.
또한, 본 발명은 압타머 코팅된 금 나노입자 층을 전하 저장층으로 포함하는 유기 메모리 캐패시터 소자를 제공한다. The present invention also provides an organic memory capacitor device comprising an aptamer coated gold nanoparticle layer as a charge storage layer.
또한, 본 발명은 유기 메모리 캐패시터 소자의 바이오센서로서의 용도에 관한 것으로, 본 발명의 바이오센서는 압타머 코팅된 금 나노입자 층을 전하 저장층으로 구비하고, 상기 전하 저장층의 정전 용량을 측정함으로써 타겟 물질을 검출하는 것을 특징으로 한다.
In addition, the present invention relates to the use of the organic memory capacitor device as a biosensor, the biosensor of the present invention comprises an aptamer-coated gold nanoparticle layer as a charge storage layer, by measuring the capacitance of the charge storage layer And detecting the target substance.
본 발명의 제조방법에 따르면, 금 나노입자를 이용하는 메모리 소자를 압타머 결합을 이용하여 간단하고 용이한 공정으로 제조할 수 있다. 또한, 본 발명은 압타머 코팅된 금 나노입자를 전하 저장층으로 구비하는 캐패시터 타입의 메모리 소자 및 이를 이용한 바이오센서를 제공할 수 있다.
According to the manufacturing method of the present invention, a memory device using gold nanoparticles can be manufactured in a simple and easy process using an aptamer bond. In addition, the present invention can provide a capacitor-type memory device having aptamer-coated gold nanoparticles as a charge storage layer and a biosensor using the same.
도 1은 본 발명에 따른 제조방법의 일시예를 나타낸 순서도이다.
도 2는 본 발명의 압타머 코팅된 금 나노입자를 촬영한 고해상도 주사전자현미경(HRSEM) 사진이다.
도 3은 실시예에서 제조한 메모리 소자의 구조를 보여주는 현미경 사진이다.
도 4는 실시예에서 제조한 메모리 소자의 100 kHz에서의 이력현상(hysteresis)을 나타내는 정전용량-전압 곡선이다.
도 5는 실시예에서 제조한 메모리 소자의 1 MHz에서의 이력현상(hysteresis)을 나타내는 정전용량-전압 곡선이다. 1 is a flow chart showing an example of a manufacturing method according to the present invention.
FIG. 2 is a high resolution scanning electron microscope (HRSEM) photograph of the aptamer coated gold nanoparticles of the present invention.
3 is a micrograph showing the structure of the memory device manufactured in Example.
4 is a capacitance-voltage curve showing hysteresis at 100 kHz of the memory device fabricated in the example.
FIG. 5 is a capacitance-voltage curve showing hysteresis at 1 MHz of the memory device fabricated in the example. FIG.
이하, 도 1을 참고하여 본 발명의 제조방법을 자세히 설명한다.
Hereinafter, the manufacturing method of the present invention will be described in detail with reference to FIG. 1.
먼저, 실리콘 산화막(2)이 증착된 기판(1) 표면을 아민기를 갖는 실란 화합물로 기능화시켜 아민기를 갖는 실란 화합물 층(3)을 형성한다(S1 단계).First, the surface of the
바람직하게는, 아민기를 갖는 실란 화합물은 3-아미노프로필트라이에톡시실란(APTES) 등이 있으며, 이에 한정되는 것은 아니다. Preferably, the silane compound having an amine group includes 3-aminopropyltriethoxysilane (APTES) and the like, but is not limited thereto.
본 발명의 일 실시예에 따르면, S1 단계는 실리콘 산화막이 증착된 기판을 수산화나트륨(NaOH)으로 처리하여 기판 표면을 히드록시기로 개질시킨 후 3-아미노프로필트리에톡시실란(APTES) 용액에 함침시킨다. 이때, 기판 표면의 히드록시기(-OH)와 아미노기를 갖는 실란 화합물과의 -O-Si- 결합의 형성을 통해 아민기가 기판 표면의 말단에 존재하게 된다. According to an embodiment of the present invention, the step S1 is performed by treating a substrate on which a silicon oxide film is deposited with sodium hydroxide (NaOH) to modify the surface of the substrate with a hydroxyl group, and then impregnating the solution with 3-aminopropyltriethoxysilane (APTES). . At this time, the amine group exists at the terminal of the substrate surface through the formation of -O-Si- bond between the hydroxyl group (-OH) on the substrate surface and the silane compound having an amino group.
본 발명의 다른 실시예에 따르면, S1 단계는 실리콘 산화막이 증착된 기판을 UV-오존 처리한 후 3-아미노프로필트리에톡시실란(APTES) 용액에 함침시킨다. 이때, UV-오존 처리에 의해 생성된 기판 표면의 히드록시기(-OH)와 아미노기를 갖는 실란 화합물과의 -O-Si- 결합의 형성을 통해 아민기가 기판 표면의 말단에 존재하게 된다. According to another embodiment of the present invention, the step S1 is impregnated with a 3-aminopropyltriethoxysilane (APTES) solution after UV-ozone treatment of the substrate on which the silicon oxide film is deposited. At this time, the amine group is present at the end of the substrate surface through the formation of an —O—Si— bond between the hydroxyl group (—OH) on the surface of the substrate generated by UV-ozone treatment and the silane compound having an amino group.
다음으로, S1 단계에서 아민기로 기능화된 기판 표면을 숙신산 무수물로 처리하고 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드 용액과 N-하이드록시숙신이미드로 코팅한다(S2 단계). 본 발명에서 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드와 N-하이드록시숙신이미드는 이후 압타머에 특이적으로 결합하는 단백질 (PSMA: prostate specific membrane antigen)을 붙이기 위한 우수한 이탈기(반응에서 단백질이 붙기 용이하게 중간체로 붙이는 화학구조물)를 만들기 위한 목적으로 사용된다. Next, the surface of the substrate functionalized with an amine group in step S1 is treated with succinic anhydride and coated with 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution and N-hydroxysuccinimide (step S2). ). In the present invention, 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide and N-hydroxysuccinimide are excellent for attaching a protein (PSMA: prostate specific membrane antigen) that specifically binds to aptamer. It is used to create leaving groups (chemical structures that are attached as intermediates to facilitate the attachment of proteins in reactions).
본 발명의 일 실시예에 따르면, 아민기로 기능화된 기판을 숙신산 무수물로 처리하여 카르복실기로 기능화하고, 0.2 mM 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드 용액에 30분간 함침시켜 코팅하고, 0.3 mM N-하이드록시숙신이미드 용액에 30분간 함침시켜 코팅을 수행할 수 있다. According to one embodiment of the present invention, the functionalized substrate is treated with succinic anhydride by amine group functionalized with carboxyl group, and impregnated with 0.2 mM 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution for 30 minutes. The coating can be carried out by coating and impregnating 0.3 mM N-hydroxysuccinimide solution for 30 minutes.
이후, 기판 표면에 전립선 특이적 막 단백질 항원(PSMA 단백질)을 결합시켜 PSMA 단백질 층(5)을 형성한다(S3 단계). 전립선 특이적 막 단백질 항원인 PSMA 단백질은 압타머와의 고정물질로 사용된다. Thereafter, a prostate specific membrane protein antigen (PSMA protein) is bound to the substrate surface to form a PSMA protein layer 5 (step S3). PSMA protein, a prostate specific membrane protein antigen, is used as an anchor with aptamers.
본 발명의 일 실시예에 따르면, 본 단계는 0.1~100 ㎍/㎖ 농도의 전립선 특이적 막 단백질 항원 용액에 5시간 동안 함침시킴으로써 수행할 수 있다. According to one embodiment of the present invention, this step can be carried out by impregnating a prostate specific membrane protein antigen solution at a concentration of 0.1-100 μg / ml for 5 hours.
다음으로, PSMA 단백질과 압타머 코팅된 금 나노입자를 결합시켜 전하 저장층(6)을 형성한다(S4 단계).Next, the PSMA protein and the aptamer-coated gold nanoparticles are combined to form a charge storage layer 6 (step S4).
본 단계에서는, PSMA 단백질 층이 형성된 기판을 압타머 코팅된 금 나노입자 용액에 함침시킴으로써 수행될 수 있고, 이때, PSMA 단백질과 압타머가 결합하여 압타머 코팅된 금 나노입자층이 형성될 수 있다. 압타머 코팅된 금 나노입자층은 메모리 소자의 전하 저장층으로 작용한다. In this step, the substrate on which the PSMA protein layer is formed may be performed by immersing the aptamer coated gold nanoparticle solution, wherein the PSMA protein and the aptamer may be combined to form an aptamer coated gold nanoparticle layer. The aptamer coated gold nanoparticle layer acts as a charge storage layer of the memory device.
압타머는 특정분자(단백질, 펩티드, 아미노산, 유/무기 화합물)와 특이적인 결합을 할 수 있는 DNA/RNA 분자로서 항체의 단점을 보완할 수 있는 분자로 잘 알려져 있으며, 고친화력(high-affinity)과 특이력(specificity), 선택성(selectivity)를 갖는 장점이 있다. 본 발명에 따르면, 압타머는 5'-GGG AGG ACG AUG CGG AUC AGC CAU GUU UAC GUC ACU CCU-(Int spacer 18)2-SH-3'의 시퀀스를 가지는 RNA로서 티올기에 의하여 자동적으로 금 나노입자에 결합될 수 있다. Aptamers are DNA / RNA molecules that can specifically bind to specific molecules (proteins, peptides, amino acids, organic / inorganic compounds) and are well known as molecules that can compensate for the shortcomings of antibodies and have high affinity. And specificity and selectivity. According to the present invention, the aptamer is a RNA having a sequence of 5'-GGG AGG ACG AUG CGG AUC AGC CAU GUU UAC GUC ACU CCU- (Int spacer 18) 2-SH-3 'and is automatically linked to gold nanoparticles by a thiol group. Can be combined.
바람직하게는, 압타머 코팅된 금 나노입자는 티올기를 함유하는 폴리에틸렌글리콜로 추가 코팅시킨 것을 사용한다. 이때, 티올기가 달린 폴리에틸렌글리콜(poly ethylene glycol-SH)이 압타머가 붙지 않은 자리에 부착됨으로서 금 나노입자의 빈 공간을 채울 수 있다. 빈 공간이 남지 않음으로써 압타머 코팅된 금 나노입자끼리의 엉겨붙음을 방지하는 효과가 있다.Preferably, the aptamer coated gold nanoparticles are those further coated with polyethylene glycol containing thiol groups. In this case, the polyethylene glycol with a thiol group (polyethylene glycol-SH) can be attached to the place where the aptamer is not attached to fill the empty space of the gold nanoparticles. Since no empty space is left, the aptamer-coated gold nanoparticles are prevented from being entangled with each other.
금 나노입자의 직경은 5∼20 ㎚이고, 바람직하게는 5~10 ㎚이다. 금 나노입자의 직경이 5 nm 미만이면 나노입자의 밴드갭이 증가하여 고정된 절연막의 밴드갭을 감안할 때 입자와 입자 사이의 전도가 증가할 수 있으며, 금 나노 입자의 직경이 20 nm 초과하면, 입자의 균등성이 떨어져 메모리 소자의 문턱 전압의 불안정성(산포의 증가)이 유발되는 문제가 있어 바람직하지 않다. The diameter of gold nanoparticles is 5-20 nm, Preferably it is 5-10 nm. When the diameter of the gold nanoparticles is less than 5 nm, the band gap of the nanoparticles increases, so that the conduction between the particles and the particles may increase in view of the band gap of the fixed insulating film. When the diameter of the gold nanoparticles exceeds 20 nm, It is not preferable because there is a problem that the uniformity of particles is degraded, thereby causing instability (increasing dispersion) of the threshold voltage of the memory device.
마지막으로, 유기 반도체 층(7) 및 전극(8)을 형성하여 메모리 소자를 제조한다(S5 단계).Finally, the
본 발명에 따른 제조방법의 S5 단계는 본 기술 분야에서 공지된 임의의 방식으로 수행할 수 있다. 또한, 유기 반도체 및 전극은 본 기술 분야에서 공지된 물질로부터 통상의 지식을 가진 자가 적절하게 선택하여 사용할 수 있다. 예컨대, 유기 반도체는 펜타센, 폴리(3,4-에틸렌디옥시티오펜), 폴리티에닐렌비닐렌, 올리고티오펜 등의 유기물을 사용할 수 있으며, 전극은 금을 사용할 수 있으나, 이에 한정되는 것은 아니다.
Step S5 of the production method according to the invention can be carried out in any manner known in the art. In addition, the organic semiconductor and the electrode can be appropriately selected and used by those skilled in the art from materials known in the art. For example, the organic semiconductor may be organic materials such as pentacene, poly (3,4-ethylenedioxythiophene), polythienylenevinylene, oligothiophene, and the electrode may be gold, but is not limited thereto. .
또한, 본 발명은 압타머 코팅된 금 나노입자 층을 전하 저장층으로 포함하는 메모리 소자를 제공한다. 본 발명에 따른, 메모리 소자는 압타머 코팅된 금 나노입자 층에 전하가 저장되는 캐패시터 타입의 메모리 소자이다. The present invention also provides a memory device comprising an aptamer coated gold nanoparticle layer as a charge storage layer. According to the present invention, a memory device is a capacitor type memory device in which charge is stored in an aptamer coated gold nanoparticle layer.
또한, 본 발명은 압타머 코팅된 금 나노입자 층을 전하 저장층으로 구비하고, 상기 전하 저장층의 정전 용량을 측정함으로써 타겟 물질을 검출하는 것을 특징으로 하는 바이오 센서를 제공한다. 본 발명에 따른 압타머를 이용한 바이오 센서는 압타머와 특이적으로 결합하는 특정 단백질(타겟 물질)이 압타머에 노출되었을 때 나타나는 금 나노입자 층(전하 저장층)의 정전 용량을 측정함으로써 타겟 물질의 검출이 가능하다.
The present invention also provides a biosensor comprising an aptamer-coated gold nanoparticle layer as a charge storage layer and detecting a target material by measuring the capacitance of the charge storage layer. The biosensor using the aptamer according to the present invention is a target material by measuring the capacitance of the gold nanoparticle layer (charge storage layer) that appears when a specific protein (target material) that specifically binds to the aptamer is exposed to the aptamer. Can be detected.
이하에서는, 본 발명의 구성을 실시예를 들어 더욱 상세히 설명하지만, 본 발명의 권리범위가 하기 실시예로만 한정되는 것은 아니다.
Hereinafter, the structure of the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited to the following examples.
실시예 Example
PSMA 단백질을 카르복실화된 실리콘 옥사이드 표면에 결합시킨다. 먼저, 10 nm 두께의 실리콘 산화막(SiO2)이 증착된 기판 표면에 NaOH로 처리하여 하이드록시기로 기능화시켰다. 이후, 3-아미노프로필 트리에톡시실란(APTES) 용액(에탄올 중 5%)에 함침시켜 기판 표면을 아미노-기능화(SiO2-NH2)하였다. 이후, 디메틸포름아마이드(DMF) 중 무수 숙신산 용액(0.05M)으로 처리함으로써 기판 표면을 카르복실화하였다. 카르복실화된 기판 표면에 PSMA를 결합시키기 위해서, 0.2 mM 탈이온수 중 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드(EDC) 용액 2 mL에 30분 동안 온화하게 딥 코팅하였다. 이후, 0.3 mM NHS 2 ㎖로 30분 동안 딥 코팅하였다. PSMA 단백질을 최종 농도가 10 ㎍/㎖가 되도록 첨가한 후 5시간 동안 딥 코팅하였다. 금(Au) 나노입자를 폴리에틸렌 글리콜 350으로 코팅하였다. 금 나노입자의 표면을 압타머로 기능화하였다. 압타머로 코팅된 금 나노입자를 촬영한 사진을 도 2에 나타냈다. Au 나노입자의 평균 직경 크기는 16 ㎚였다. 이후, 펜타센 반도체층 및 금 전극(0.5 ㎜ 직경)을 각각 20 ㎚ 두께로 열 증발증착법에 의해 증착하여 본 발명의 유기 캐패시터 메모리 소자를 제조하였다. 제조된 메모리 소자의 구조를 나타내는 현미경 사진을 도 3에 나타냈다.
The PSMA protein is bound to the carboxylated silicon oxide surface. First, a 10 nm-thick silicon oxide film (SiO 2 ) was treated with NaOH on the surface of the substrate, and functionalized with a hydroxyl group. Subsequently, the substrate surface was amino-functionalized (SiO 2 —NH 2 ) by impregnation with a 3-aminopropyl triethoxysilane (APTES) solution (5% in ethanol). The substrate surface was then carboxylated by treatment with a succinic anhydride solution (0.05M) in dimethylformamide (DMF). To bind PSMA to the carboxylated substrate surface, gently dip coating for 30 minutes in 2 mL of a solution of 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide (EDC) in 0.2 mM deionized water. . Thereafter, dip coating was performed with 2 ml of 0.3 mM NHS for 30 minutes. PSMA protein was added to a final concentration of 10 μg / ml and then dip coated for 5 hours. Gold (Au) nanoparticles were coated with polyethylene glycol 350. The surface of the gold nanoparticles was functionalized with aptamers. A photograph of gold nanoparticles coated with an aptamer is shown in FIG. 2. The average diameter size of Au nanoparticles was 16 nm. Thereafter, the pentacene semiconductor layer and the gold electrode (0.5 mm diameter) were deposited by thermal evaporation deposition to a thickness of 20 nm, respectively, to manufacture an organic capacitor memory device of the present invention. A micrograph showing the structure of the manufactured memory device is shown in FIG. 3.
시험예Test Example
100 kHz 및 1 MHz의 주파수에서 HP Agilent 4284A를 사용하여 C-V 성능을 측정하여 그 결과를 각각 도 4 및 도 5에 나타냈다. 도 4 및 도 5로부터, 압타머 코팅된 금 나노입자의 전하 저장층으로 역할을 C-V 성능의 이력현상(hysteresis)으로부터 확인할 수 있다.
CV performance was measured using the HP Agilent 4284A at frequencies of 100 kHz and 1 MHz and the results are shown in FIGS. 4 and 5, respectively. 4 and 5, it can be seen from the hysteresis of CV performance to serve as a charge storage layer of aptamer coated gold nanoparticles.
1: P형 실리콘 기판 2: 실리콘 산화막
3: 3-아미노프로필 트리에톡시실란(APTES) 층
4: N-하이드록시숙신이미드 및 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드 층
5: PSMA 단백질 층
6: 압타머 코팅된 금 나노입자 층(전하저장층)
7: 유기 반도체층(펜타센) 8: 금 전극1: P-type silicon substrate 2: Silicon oxide film
3: 3-aminopropyl triethoxysilane (APTES) layer
4: N-hydroxysuccinimide and 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide layer
5: PSMA protein layer
6: aptamer coated gold nanoparticle layer (charge storage layer)
7: organic semiconductor layer (pentacene) 8: gold electrode
Claims (9)
(S2) S1 단계에서 아민기로 기능화된 기판 표면을 숙신산 무수물로 처리하고 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드 용액과 N-하이드록시숙신이미드로 코팅하는 단계;
(S3) 상기 기판 표면에 PSMA 단백질(전립선 특이적 막 단백질 항원)을 결합시키는 단계;
(S4) 상기 PSMA 단백질과 압타머 코팅된 금 나노입자를 결합시켜 전하 저장층을 형성하는 단계; 및
(S5) 유기 반도체 층 및 전극을 형성하는 단계를 포함하는 유기 메모리 캐패시터 소자의 제조방법.(S1) treating the substrate on which the silicon oxide film is deposited with a silane compound having an amine group to functionalize the surface of the substrate with an amine group;
(S2) treating the surface of the substrate functionalized with an amine group in step S1 with succinic anhydride and coating with 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution and N-hydroxysuccinimide;
(S3) binding a PSMA protein (prostate specific membrane protein antigen) to the substrate surface;
(S4) combining the PSMA protein with the aptamer coated gold nanoparticles to form a charge storage layer; And
(S5) A method of manufacturing an organic memory capacitor device comprising forming an organic semiconductor layer and an electrode.
상기 S1 단계는 실리콘 산화막이 증착된 기판을 수산화나트륨(NaOH) 또는 UV-오존으로 처리하여 히드록시기로 개질시킨 후 3-아미노프로필트리에톡시실란(APTES) 용액에 함침시켜 기판 표면을 아민기로 기능화시키는 것을 특징으로 하는 유기 메모리 캐패시터 소자의 제조방법.The method according to claim 1,
In the step S1, the substrate on which the silicon oxide film is deposited is treated with sodium hydroxide (NaOH) or UV-ozone, modified with a hydroxyl group, and then impregnated in 3-aminopropyltriethoxysilane (APTES) solution to functionalize the surface of the substrate with an amine group. A method of manufacturing an organic memory capacitor device, characterized in that.
상기 S2 단계는 아민기로 기능화된 기판을 숙신산 무수물로 처리하고, 0.2 mM 1-에틸-3-(3-디메틸아미노프로필)-카보디이미드 용액에 30분간 함침시켜 코팅하고, 0.3 mM N-하이드록시숙신이미드 용액에 30분간 함침시켜 코팅하는 것을 특징으로 하는 유기 메모리 캐패시터 소자의 제조방법.The method according to claim 1,
The step S2 is treated by treating the substrate functionalized with an amine group with succinic anhydride, impregnated with a 0.2 mM 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide solution for 30 minutes, and coated with 0.3 mM N-hydroxy. A method of manufacturing an organic memory capacitor device, characterized in that the coating is impregnated with succinimide solution for 30 minutes.
상기 S3 단계는 0.1~100 ㎍/㎖ 농도의 PSMA 단백질 용액에 5시간 동안 함침시키는 것을 특징으로 하는 유기 메모리 캐패시터 소자의 제조방법.The method according to claim 1,
The step S3 is a method of manufacturing an organic memory capacitor device, characterized in that the impregnated for 0.1 hours to 0.1 ~ 100 ㎍ / ㎖ PSMA protein solution.
상기 S4 단계의 압타머 코팅된 금 나노입자는 티올기 함유 폴리에틸렌글리콜로 추가 코팅시킨 것을 특징으로 하는 유기 메모리 캐패시터 소자의 제조방법. The method according to claim 1,
The aptamer-coated gold nanoparticles of step S4 is a method of manufacturing an organic memory capacitor device, characterized in that the additional coating with a thiol group-containing polyethylene glycol.
상기 S4 단계의 금 나노입자는 직경이 5~20 ㎚인 것을 특징으로 하는 유기 메모리 캐패시터 소자의 제조방법. The method according to claim 5,
The gold nanoparticles of step S4 is a manufacturing method of an organic memory capacitor device, characterized in that the diameter of 5 ~ 20nm.
상기 S5 단계의 유기 반도체층은 펜타센, 폴리(3,4-에틸렌디옥시티오펜), 폴리티에닐렌비닐렌 및 올리고티오펜으로 이루어지는 군으로부터 선택되는 것을 특징으로 하는 유기 메모리 캐패시터 소자의 제조방법. The method according to claim 1,
Wherein the organic semiconductor layer of step S5 is selected from the group consisting of pentacene, poly (3,4-ethylenedioxythiophene), polythienylenevinylene and oligothiophene.
상기 전하 저장층의 정전 용량을 측정함으로써 타겟 물질을 검출하는 것을 특징으로 하는 바이오센서. Equipped with aptamer coated gold nanoparticle layer as a charge storage layer,
And detecting a target material by measuring the capacitance of the charge storage layer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120026697A KR101377053B1 (en) | 2012-03-15 | 2012-03-15 | Memory capacitor device including aptamer coated au nanoparticle layer and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120026697A KR101377053B1 (en) | 2012-03-15 | 2012-03-15 | Memory capacitor device including aptamer coated au nanoparticle layer and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20130104820A true KR20130104820A (en) | 2013-09-25 |
| KR101377053B1 KR101377053B1 (en) | 2014-03-25 |
Family
ID=49453591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020120026697A KR101377053B1 (en) | 2012-03-15 | 2012-03-15 | Memory capacitor device including aptamer coated au nanoparticle layer and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101377053B1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020071837A1 (en) * | 2018-10-05 | 2020-04-09 | 씨제이제일제당 (주) | Memory device comprising biocompatible polymer nanoparticles, and manufacturing method therefor |
| WO2020235697A1 (en) * | 2019-05-17 | 2020-11-26 | 주식회사 넥스모스 | Improved method for manufacturing microneedle-based diagnostic skin patch coated with aptamer, and patch |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102018177B1 (en) | 2018-11-26 | 2019-09-04 | 명지대학교 산학협력단 | System for monitoring radiation based on multiple arrays of silicon photomultipliers |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101009938B1 (en) | 2008-10-24 | 2011-01-20 | 포항공과대학교 산학협력단 | Aptamer-based silicon nanowire biosensor for cancer diagnoses based on detection of?vegf, and method of manufacturing the same and detecting vegf using the same |
-
2012
- 2012-03-15 KR KR1020120026697A patent/KR101377053B1/en active IP Right Grant
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020071837A1 (en) * | 2018-10-05 | 2020-04-09 | 씨제이제일제당 (주) | Memory device comprising biocompatible polymer nanoparticles, and manufacturing method therefor |
| KR20200039198A (en) | 2018-10-05 | 2020-04-16 | 씨제이제일제당 (주) | Memory device including nanopaticle of biodegradable polymer and manufacturing method thereof |
| CN113678272A (en) * | 2018-10-05 | 2021-11-19 | Cj第一制糖株式会社 | Memory device comprising biocompatible polymer nanoparticles and method of manufacturing the same |
| JP2022504347A (en) * | 2018-10-05 | 2022-01-13 | シージェイ チェイルジェダン コーポレーション | Memory device containing biodegradable polymer nanoparticles and its manufacturing method |
| CN113678272B (en) * | 2018-10-05 | 2024-01-02 | Cj第一制糖株式会社 | Memory device comprising biocompatible polymer nanoparticles and method of manufacturing the same |
| WO2020235697A1 (en) * | 2019-05-17 | 2020-11-26 | 주식회사 넥스모스 | Improved method for manufacturing microneedle-based diagnostic skin patch coated with aptamer, and patch |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101377053B1 (en) | 2014-03-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7124317B2 (en) | Semiconductor sensors and compound sensors | |
| US8901620B2 (en) | Biosensor comprising reduced graphene oxide layer | |
| US9162885B2 (en) | Graphene-encapsulated nanoparticle-based biosensor for the selective detection of biomarkers | |
| US10989684B2 (en) | Biosensor, process for its preparation and method for detecting an analyte using the biosensor | |
| US20170273608A1 (en) | Ionic barrier for floating gate in vivo biosensors | |
| KR101979225B1 (en) | Graphene Transistor including Functionalized N-heterocyclic Carbene compound and Process for producing of the same, Bio Sensor comprising thereof | |
| US8999739B2 (en) | Field effect transistor-based bio-sensor | |
| Li et al. | Surface molecularly imprinted polymers-based electrochemical sensor for bovine hemoglobin recognition | |
| KR101377053B1 (en) | Memory capacitor device including aptamer coated au nanoparticle layer and preparation method thereof | |
| KR102084088B1 (en) | Sensor for detecting Zika virus and preparation method thereof | |
| CN104707991A (en) | Magnetic graphene oxide nano-silver composite material and preparation and application thereof | |
| KR20120125906A (en) | Method for preparing biosensor comprising reduced graphene oxide pattern using printing of self-assembled monolayer and biosensor prepared thereby | |
| KR102240669B1 (en) | Organic electrochemical transistor device and method for preparing the same | |
| Kim et al. | Robust ZnO nanoparticle embedded memory device using vancomycin conjugate and its biorecognition for electrical charging node | |
| WO2020113361A1 (en) | Functionalized black phosphorus/gold composite material and application thereof | |
| Kim et al. | Characterization of gold nanoparticle pentacene memory device with polymer dielectric layer | |
| Li et al. | Electrospun polyacrylonitrile fibers with and without magnetic nanoparticles for selective and efficient separation of glycoproteins | |
| US20240182669A1 (en) | Mixed functionalized graphene structure and corresponding field-effect transistor biosensor | |
| Huang et al. | Development of all-solution-processed nanocrystal memory | |
| TWI728491B (en) | Memory device including nanoparticle of biodegradable polymer and manufacturing method thereof | |
| KR101740784B1 (en) | Bisphenol A aptamer-functionalized urchin-like conducting polymer nanoparticles for ultrasensitive field-effect-transistor endocrine-disruptor sensor | |
| Jung et al. | Charging effect in Au nanoparticle memory device with biomolecule binding mechanism | |
| Rao et al. | Bottom-up meets top down: An integrated approach for nano-scale devices | |
| KR20180055094A (en) | Method for the surface modification of thin flim active layer in semiconductor based biosensor | |
| JP5447233B2 (en) | Sensor and manufacturing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E601 | Decision to refuse application | ||
| X091 | Application refused [patent] | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20170504 Year of fee payment: 4 |
|
| FPAY | Annual fee payment |
Payment date: 20180307 Year of fee payment: 5 |
|
| FPAY | Annual fee payment |
Payment date: 20191125 Year of fee payment: 7 |