TWI273237B - Coulomb blockade device operated under room temperature - Google Patents
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五、發明說明(1) 【發明所屬之技術領域】 A本發明係有關於一種半導體裝置,特別是有關於 在至溫下具有庫倫阻斷效應的裝置及其製造方法。 【先前技術】 近年來,利用矽製程製造分子裝置的技術已逐漸 視,然而,雖業界在製程改善及分子組裝技術上投入重 心力,但由於裝置快速微縮至奈米級尺寸,須配合弓丨少 的先進材料或開發新的製造技術,遂仍有許多製^ ,靳 停留在開發階段並不成熟。目前,類似單電子電晶體方還 置由於其可在低功率條件下操作少量電子的優點,已的裝 製造高密度積體電路的指標性技術,然為使該等裝置成為 實用價值,必須允許在室溫條件下可正常操作,而為具備 達成此目的,裝置中的島結構尺寸需小於丨0奈米,^配合 整體電容及減少熱擾亂的效應。 降低 目前可知由生物分子建構的裝置其具有自動組裝、 米級尺寸及低成本等的優點,此外,現階段的生物^ 奈 術(例如DNA感測裝置)係利用探針DNA雜交目標DNa來析技 行,而此處的探針DNA需在3,或5,端進行標記,但由於 射性同位素或32P等半衰期元素對人體有潛在危險,故;玫 上已發展出其他的標記方式,如化學發光標記、鸯光:場 標記等,不過以上方法仍需配合昂貴的探針和光學檢木色 統,且要將樣本DN A固定於薄膜上,方能使其與探針雜則系 合,不但耗時且常常造成使用者不便。 ”V. INSTRUCTION DESCRIPTION OF THE INVENTION (1) Technical Field of the Invention A The present invention relates to a semiconductor device, and more particularly to an apparatus having a Coulomb blocking effect at a temperature and a method of manufacturing the same. [Prior Art] In recent years, the technology for manufacturing molecular devices using the tantalum process has been gradually observed. However, although the industry has invested heavily in process improvement and molecular assembly technology, it has to be matched with bows due to the rapid shrinkage of the device to the nanometer size. With less advanced materials or the development of new manufacturing technologies, there are still many systems that are not mature enough to stay in the development stage. At present, similar single-electron transistors are still placed because of their advantages of being able to operate a small amount of electrons under low-power conditions, and the already-imported technology for manufacturing high-density integrated circuits, in order to make these devices practical, must be allowed It can be operated normally at room temperature, and in order to achieve this, the size of the island structure in the device needs to be less than 丨0 nm, which matches the overall capacitance and reduces the effect of thermal disturbance. It is known that the device constructed by biomolecules has the advantages of automatic assembly, rice size and low cost. In addition, the current biotechnology (such as DNA sensing device) utilizes probe DNA hybridization target DNa to analyze the technique. However, the probe DNA here needs to be labeled at the 3, or 5, end, but due to the potential danger of the semi-life elements such as radioisotope or 32P, other marking methods have been developed, such as chemistry. Luminous mark, 鸯 light: field mark, etc., but the above method still needs to cooperate with expensive probes and optical inspection color, and the sample DN A should be fixed on the film to make it fit with the probe. Not only is it time consuming and often causes inconvenience to the user. ”
1273237 五、發明說明(2) 【發明内容】 有鑑於此’本發明之目的係揭露一種庫偷阻斷裝置, 其可在至/jnL下操作,且D N A模板可快速、靈敏地辨識目標 DNA序列。 ' 為了達成上述目的,本發明提供一種室溫操作之庫倫 阻斷裝置,包括:一基板;一氧化層,形成於該基板上; 一源極以及一汲極,設置於該氧化層上;一第一金奈米粒 子,固定於該氧化層上且位於該源極與該汲極之間;以及 一第二金奈米粒子,位於該第一金奈米粒子上方,且該第 一與第二金奈米粒子間係以一雜交去氧核醣核酸(hybrid DNA)連接,其中該雜交去氧核醣核酸係由一抓取去氧核醣 核酸(capture DNA)、一探針去氧核醣核酸(pr〇be DN/)以 及一目標去氧核醣核酸(target DNA)所組成,該抓取DNA 之一端係與該探針DNA之一端連接以形成一股由抓取DNa與 探針DNA所組成之去氧核醣核酸,該股由抓取 DNA與探 針DNA所組成之去氧核醣核酸並與該目標麗a互補以形成一 雙之雜父去氣核釀核酸。 為了達成上述目的,本發明另提供一種室溫操作之庫 倫阻斷裝置之製造方法,包括下列步驟:提供一基板,該 基板上形成有一氧化層;設置一源極與一汲極於該氧化^ 上;固定一第一金奈米粒子於該氧化層上且使其位於該^ 極,該汲極之間;形成一與該第一金奈米粒子連接之雜交 去氧核醣核酸;以及於該第一金奈米粒子上方形成一第二1273237 V. SUMMARY OF THE INVENTION (2) In view of the above, the object of the present invention is to disclose a library stealing device which can operate at up to /jnL, and the DNA template can quickly and sensitively identify the target DNA sequence. . In order to achieve the above object, the present invention provides a room temperature operated Coulomb blocking device comprising: a substrate; an oxide layer formed on the substrate; a source and a drain disposed on the oxide layer; a first gold nanoparticle fixed on the oxide layer between the source and the drain; and a second gold nanoparticle located above the first gold nanoparticle, and the first and the first The two gold nanoparticles are linked by a hybrid DNA, wherein the hybrid DNA is captured by a capture DNA, a probe DNA (pr 〇be DN/) and a target DNA, one end of the grab DNA is ligated to one end of the probe DNA to form a strand consisting of the capture DNa and the probe DNA. Oxyribonucleic acid, which is a DNA consisting of DNA and probe DNA, and complementary to the target, to form a pair of heterogeneous denuclear nucleic acids. In order to achieve the above object, the present invention further provides a method for manufacturing a Coulomb blocking device operating at room temperature, comprising the steps of: providing a substrate on which an oxide layer is formed; and providing a source and a drain for the oxidation. Fixing a first gold nanoparticle on the oxide layer and positioning it between the anode and the drain; forming a hybrid deoxyribonucleic acid linked to the first gold nanoparticle; Forming a second above the first gold nanoparticle
0522-A20466TWF(Ν2);dav i d.p td 第7頁 1273237 ------ 五、發明說明(3) 金奈米粒子’且該第一與第二金奈米粒子間以該雜交去氧 核_核酸連接。 為讓本發明之上述目的、特徵及優點能更明顯易懂, 下文特舉一較佳實施例,並配合所附圖式,作詳細說明如 下: 【實施方式】 本發明庫倫阻斷裝置的製作包括下列步驟:(丨)金奈 米粒子的合成,(2 )金奈米電極的製作,(3)單層金奈米粒 子的固定,以及(4 )DNA雜交及複層金奈米粒子的自組裝。 (1)金奈米粒子的合成:首先,將四氯金酸(hauci4)溶 於去離子水中,以製備一四氯金酸水溶液,接著,將三納 檸檬酸鹽(trisodium citrate)、丹寧酸(tannic acid)以 及碳酸鉀(potassium carbonate)溶於另一去離子水中, 以製備一擰檬酸水溶液,接著,將兩溶液分別加熱後相互 此s並強烈稅拌’待混合溶液出現深紅顏色後,加熱至沸 騰,、即形成一金奈米粒子溶液。該金奈米粒子溶液的吸收 光譜係由Hitachi U33 10 UV-vis光譜儀測量之,而金奈米 粒子的大小則由高解析度的穿透式電子顯微鏡(HR —TE/ ” model H-700,Hitachi)加以評估。金奈米粒子的半徑大 小可由三鈉檸檬酸鹽(trisodium citrate)、丹宜酸 (tannic acid)以及四氯金酸的添加量加以控制了如當 添加較大量的三鈉擰檬酸鹽或丹寧酸時,可曰 .,, 」」付尺寸較小的 金奈米粒子,反之,則會得到尺寸較大的金太0522-A20466TWF(Ν2); dav i dp td Page 7 1273237 ------ V. Description of the invention (3) The gold nanoparticles 'and the deoxygenated by the hybrid between the first and second gold nanoparticles Nuclear-nucleic acid linkage. The above described objects, features, and advantages of the present invention will be apparent from the following description of the preferred embodiments. Including the following steps: (丨) synthesis of gold nanoparticles, (2) fabrication of gold nanoparticles, (3) fixation of single-layered gold nanoparticles, and (4) DNA hybridization and multi-layered gold nanoparticles Self-assembly. (1) Synthesis of gold nanoparticles: First, tetrachloroauric acid (hauci4) is dissolved in deionized water to prepare a tetrachloroauric acid aqueous solution, followed by trisodium citrate and tannin. The acid (tannic acid) and potassium carbonate are dissolved in another deionized water to prepare an aqueous solution of citric acid. Then, the two solutions are separately heated and then mixed with each other and strongly taxed. Thereafter, it is heated to boiling, that is, a gold nanoparticle solution is formed. The absorption spectrum of the gold nanoparticle solution was measured by a Hitachi U33 10 UV-vis spectrometer, while the size of the gold nanoparticles was measured by a high-resolution transmission electron microscope (HR-TE/" model H-700. Hitachi). The radius of the gold nanoparticles can be controlled by the addition of trisodium citrate, tannic acid and tetrachloroauric acid, such as when adding a larger amount of trisodium. When citrate or tannic acid is used, 金.,, ”" can be used to pay smaller size gold nanoparticles, and vice versa.
1273237 五、發明說明(4) 利用(化2)Λ奈Λ電極的製作··首★,提供一基板,接著, 惫爲二軋目/儿積法(C V D )沉積一氧化層於該基板上,該 #於二j厚度大體介於150〜250奈米,之後,覆蓋一光阻 二‘ 2,化層上,該光阻層的厚度大體為2 0 0〜6 0 0奈米, ^, 、/00奈/卡’接著,圖案化該光阻層以獲得電極圖 二μ 2後二祭鍍一作為黏著層的金屬鈦層於該圖案化光阻 二人二覆蓋該等電極圖案,以增加該氧化層與未來欲沉積 丰、間的黏著力,該金屬鈦層的厚度大體介於丨〜丨〇奈 佳為5奈米,接I,蒸鍍一金膜於該金屬鈦層上, 的厚度大體介於40〜80奈米,較佳為6〇奈米,最後, -丙酮/合液清洗該基板以剝除剩餘光阻,至此,即完成 奈米電極的製作。金奈米電極係由金所構成,其包括 、;’、虽與;及極,或包括一源極、一汲極與一閘極,其中 ,極與汲極的距離大體介於10〜6 50奈米,較佳為30 0奈、 只’而閑極與源極或汲極的距離大體介於1 000 ~2000卉 上佳:i1、5 00奈米:該等金奈米電極的寬度大體介於 在腔沾同丁米’較佳為6 00奈米’而該等電極的厚度即為 金膜的厚m度,大體介於40〜80奈米’較佳為6〇奈米。 (3 )單層金奈米粒子的固定:此步驟係利用一 =奈”子固定於氧化層上。以下即說明該連接分子 的1作:百先,取特定量的連接分子溶於二甲亞楓 =er;4yl/:Txide,誦)溶劑中,之後,調整該溶液 /辰度至特疋浪度,即完成此連接分子溶液的製備,苴 連接分子一端為矽烷基而另一端為含硫基。以下開ς進g 0522-A20466TWF(N2);david.ptd 第9頁 1273237 五、發明說明(5) ^層金奈来粒子的固定,首先,將設有金奈米電極的基板 次入攝氏1 0 0度的連接分子溶液中,使連接分子含矽烷基 的一端與氧化層形成矽烷鍵的鍵結,之後,取出該基板以 DMSO清洗並用氮氣吹乾,接著,將基板浸入金奈米粒子溶 液中反應隔夜,則連接分子含硫基的另一端即會與金奈米 粒子產生連接,至此,即完成金奈米粒子藉由連^分&固 定於氧化層上的步驟,本發明中,固定後的金奈米粒子係 位於源極與汲極間的氧化層上。 (4 )DNA雜交及複層金奈米粒子的自組裝··首先,將抓 取DNA(capture DNA,cDNA)溶液注入N — 2-羥乙基對二氮己 環,N-2-乙石黃酸(4-(2-hydroxyethyl)-l- piperazineethanesulfonic acid,HEPES)溶液中以形成 一混合溶液,該HEPES溶液的pH值係藉由EDTA緩衝溶液調 整之’接著’將固定有單層金奈米粒子的基板浸入該混合 溶液中於室溫下反應,以使金奈米粒子與cDNA產生連接, 續以SPSC缓衝溶液清洗,以去除未與金奈米粒子鍵結的 cDNA分子,之後,再利用氮氣吹乾,即產生抓取DNA藉由 其所包含的一含硫基與金奈米粒子連接的情形,上述連接 過程係為一自組裝(se 1 f - as semb ly)連接過程,接著,將 該基板浸入目標DNA(target DNA,tDNA)溶液與探DNA (probe DNA,pDNA)溶液所組成的混合溶液中進行雜交反 應,之後,再以SPSC緩衝溶液清洗該基板以去除基板上的 殘留試劑,至此,即完成D N A的雜交工作,形成一包含抓 取MA、目標DNA與探針DNA的雜交DMA,其中抓取MA的一1273237 V. DESCRIPTION OF THE INVENTION (4) Using a (Chemical 2) Λ Λ Λ 的 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , The thickness of the #jjj is generally between 150 and 250 nm, and then covers a photoresist 2', and the thickness of the photoresist layer is substantially 200 to 600 nm, ^, , /00奈/卡' Next, the photoresist layer is patterned to obtain an electrode pattern of 2 μ 2 and then a metal titanium layer as an adhesive layer is coated on the patterned photoresist to cover the electrode patterns to Increasing the adhesion between the oxide layer and the future, the thickness of the metal titanium layer is generally between 5 nanometers, and I deposit a gold film on the metal titanium layer. The thickness is generally between 40 and 80 nm, preferably 6 nanometers. Finally, the substrate is washed with acetone-liquid to remove the residual photoresist, and thus the fabrication of the nano electrode is completed. The Jinnai electrode is composed of gold, which includes; ', and; and the pole, or includes a source, a drain and a gate, wherein the distance between the pole and the drain is generally between 10 and 6 50 nm, preferably 30 0 Nai, only 'the distance between the idle pole and the source or the bungee is generally between 1 000 and 2000. The best is: i1, 500 nm: the width of the gold nano electrodes Generally, the thickness of the electrodes is the thickness of the gold film, and the thickness of the electrodes is generally 40 to 80 nm, preferably 6 nanometers. (3) Fixation of single-layered gold nanoparticles: This step is fixed on the oxide layer by using a =na. The following is a description of the one of the linking molecules: a hundred first, and a specific amount of the linking molecule is dissolved in the dimethyl group. Yafeng = er; 4yl /: Txide, 诵) solvent, after which, adjust the solution / Chen to the special wave degree, that is, complete the preparation of the molecular solution of the connection, the 苴 linker molecule is 矽 alkyl at one end and Sulfur-based. The following opening into the g 0522-A20466TWF (N2); david.ptd page 9 1273237 V, invention description (5) ^ layer of gold nai particles fixed, first, will be equipped with a gold nano electrode substrate times In a solution of a linking molecule of 100 ° C, the end of the linking molecule containing a decyl group is bonded to the oxide layer to form a decane bond, and then the substrate is taken out and washed with DMSO and blown with nitrogen, and then the substrate is immersed in Chennai. In the rice particle solution, the reaction is overnight, and the other end of the linking molecule containing the sulfur group is connected to the gold nanoparticle, and thus, the step of fixing the gold nanoparticle by the bonding and the fixing on the oxide layer is performed. In the invention, the fixed gold nanoparticle system is located at the source On the oxide layer between the electrode and the bungee. (4) DNA hybridization and self-assembly of the layered gold nanoparticles. First, the capture DNA (cDNA) solution is injected into the N- 2-hydroxyethyl-p-diazepine. A solution of 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid (HEPES) is formed to form a mixed solution, and the pH of the HEPES solution is adjusted by the EDTA buffer solution. Then, the substrate with the single layer of gold nanoparticles is immersed in the mixed solution to react at room temperature, so that the gold nanoparticles are connected with the cDNA, and then washed with SPSC buffer solution to remove the non-carbonized rice. The particle-bound cDNA molecule is then blown dry with nitrogen to produce a grasping DNA by attaching a sulfur-containing group to the gold nanoparticle, and the joining process is a self-assembly (se 1 f - as semb ly) the ligation process, followed by immersing the substrate in a mixed solution of a target DNA (tDNA) solution and a probe DNA (pDNA) solution, followed by SPSC buffering The substrate is cleaned by a solution to remove residual reagents on the substrate. At this point, the hybridization of D N A is completed to form a hybrid DMA comprising the captured MA, the target DNA and the probe DNA, wherein one of the MAs is captured.
0522-A20466TWF(N2);david.ptd 第10頁0522-A20466TWF(N2);david.ptd第10页
五、發明說明(6) 1273237 端係與探針DNA的一端連接,而此兩者所組成的帅八再與目 fDNA^補形成最終的雙股雜交DNA,接著,將清洗完後的 =板浸入由金奈米粒子溶液與PBS缓衝溶液所配製成的混 a /谷液中,以使第一層的金奈米粒子與產生連接,續 以PBS^緩衝溶液清洗該基板以去除未鍵結的金奈米粒子並 利用氮氣吹乾,之後,再將該基板浸入去離子水中,待取 出,以氮氣吹乾並在真空條件下進一步烘乾,至此,即完 成複層金奈米粒子的組裝,探針DNA藉由其所包含的一含 硫基與金奈米粒子產生連接,而上述連接過程亦為一自組 裝(self-assembly)連接過程。 實施例 (1 )金奈米粒子的合成··首先,取〇· 〇1克的四氯金酸 (HAuC14,Aldrich Chem· Co·)溶於80毫升的去離子水中, 以製備一四氯金酸水溶液,接著,取〇 · 〇丨毫克的三納檸檬 酸鹽(trisodium citrate)、〇·〇5 毫克的丹寧酸(tannic acid)以及2.3 毫克的碳酸卸(potassium carbonate) (Aldrich Chem. Co·)溶於另一 20毫升的去離子水中,以 製備一彳乎橡酸水浴液’接者’將兩溶液分別加熱至攝氏g 〇 度’之後相互混合並強烈授拌,待混合溶液出現深紅顏色 後’加熱彿騰十分鐘’即形成一金奈米粒子溶液。該金奈 米粒子溶液的吸收光譜係由Hitachi U3310 UV-vis光譜儀 測I之’其在波長5 1 7奈米的位置具有很強的表面電榮^丘 / 振(surface plasma resonance, SPR),如第la 圖所示,V. INSTRUCTIONS (6) 1273237 The end system is ligated to one end of the probe DNA, and the two of them are combined with the fDNA to form the final double-stranded hybrid DNA, and then the cleaned = plate Immersed in the mixed a/valley solution prepared by the gold nanoparticle solution and the PBS buffer solution, so that the first layer of the gold nanoparticle is connected with the connection, and the substrate is washed with a PBS buffer solution to remove the The bonded gold nanoparticles are blown dry with nitrogen, and then the substrate is immersed in deionized water, to be taken out, blown dry with nitrogen and further dried under vacuum, thereby completing the multi-layered gold nanoparticle In the assembly, the probe DNA is linked to the gold nanoparticles by a sulfur-containing group contained therein, and the above-mentioned joining process is also a self-assembly joining process. EXAMPLES (1) Synthesis of gold nanoparticles First, 1 g of tetrachloroauric acid (HAuC14, Aldrich Chem Co.) was dissolved in 80 ml of deionized water to prepare a tetrachlorogold. An aqueous acid solution, followed by tri· 〇丨mg of trisodium citrate, 〇·〇 5 mg of tannic acid, and 2.3 mg of carbonate carbonate (Aldrich Chem. Co) ·) Dissolve in another 20 ml of deionized water to prepare a lyophilic acid water bath 'setter' and heat the two solutions to Celsius deg and then mix and strongly mix, until the mixed solution appears dark red After the color, 'heating the Buddha for ten minutes', a gold nanoparticle solution is formed. The absorption spectrum of the gold nanoparticle solution is measured by a Hitachi U3310 UV-vis spectrometer, which has a strong surface-plasma resonance (SPR) at a wavelength of 517 nm. As shown in the figure la,
0522-A20466TWF(N2);david.ptd 第11頁 1273237 五、發明說明(7) 而金奈米粒子的大小一 nuclei 由=解析度的穿透式電子顯微鏡 4.0土 13奈米。相較來〇L、HlUchi)加以評估,半徑大體為 A1 4 η + 9 R ^ 來5兄,若合成出來的金奈米粒子半徑 為丄4· ϋ ± 2· 6奈米睹,廿私u 半* 士 里 其強烈的SPR吸收會出現在波長5 22奈 未左右的位置,如第lb圖所示。 (2) 金奈米電極的製作:請參閱第仏圖,首先,提供 -矽基板20,接著,利用電漿加強式化學氣相沉積法 (PECVD)沉積一二氧化矽層25於矽基板2〇上(31),二氧化 石夕層2 5的厚度為2 〇 〇奈米,之後,利用旋轉塗佈法覆蓋一 光阻層30於二氧化矽層25上(S2),光阻層3〇的厚度為4〇〇 奈米’接著’利用電子束微影法(e 1 ectr〇n beam lithography)(Leica Weprint model-200 stepper,0522-A20466TWF(N2);david.ptd Page 11 1273237 V. INSTRUCTIONS (7) The size of the gold nanoparticles is nuclei by the resolution of the penetrating electron microscope 4.0 soil 13 nm. Compared with 〇L, HlUchi), the radius is roughly A1 4 η + 9 R ^ to 5 brothers, if the synthesized gold nanoparticle radius is 丄4· ϋ ± 2·6 nanometer 睹, 廿 private u The semi-*Sririch's strong SPR absorption will appear at a position around the wavelength of 22 22, as shown in Figure lb. (2) Fabrication of the gold nano electrode: Please refer to the second drawing. First, the substrate 20 is provided, and then a cerium oxide layer 25 is deposited on the ruthenium substrate 2 by plasma enhanced chemical vapor deposition (PECVD). On the upper surface (31), the thickness of the dioxide layer 2 5 is 2 Å, and then a photoresist layer 30 is coated on the ruthenium dioxide layer 25 by spin coating (S2), and the photoresist layer 3 The thickness of the crucible is 4 〇〇 nano' followed by 'e 1 ectr〇n beam lithography (Leica Weprint model-200 stepper,
Jena, Germany)圖案化光阻層3〇以獲得電極圖案35(53), 之後,蒸鍍一作為黏著層的金屬鈦層40於圖案化光阻層上 並覆蓋該等電極圖案35(S4),以增加二氧化石夕層25與未來 欲沉積的金膜間的黏著力,金屬鈦層4 〇的厚度為5奈米, 接著,蒸鍍一金膜45於金屬鈦層40上(S5),金膜45的厚度 為60奈米,最後,利用丙酮溶液清洗矽基板20 (S6)以剝除 剩餘光阻,至此,即完成該金奈米電極3 5 ’的製作。金奈 米電極3 5 ’係由金所構成,其包括一源極5 0與一汲極5 5, 其中源極50與汲極55的距離為3〇〇奈米。該等金奈米電極 (50、5 5)的寬度為600奈米,而該等電極(50、55)的厚度 即為金膜45的厚度,為60奈米。 (3) 單層金奈米粒子的固定:此步驟係利用一連接分Jena, Germany) patterning the photoresist layer 3 to obtain an electrode pattern 35 (53), and then depositing a metal titanium layer 40 as an adhesive layer on the patterned photoresist layer and covering the electrode patterns 35 (S4) In order to increase the adhesion between the dioxide layer 25 and the gold film to be deposited in the future, the thickness of the metal titanium layer 4 为 is 5 nm, and then a gold film 45 is deposited on the metal titanium layer 40 (S5). The thickness of the gold film 45 is 60 nm. Finally, the crucible substrate 20 (S6) is cleaned with an acetone solution to remove the remaining photoresist, and thus the fabrication of the gold nano electrode 35' is completed. The gold nano electrode 3 5 ' is composed of gold, and includes a source 50 and a drain 5 5 , wherein the source 50 and the drain 55 are 3 nanometers apart. The width of the gold nanoelectrodes (50, 5 5) is 600 nm, and the thickness of the electrodes (50, 55) is the thickness of the gold film 45, which is 60 nm. (3) Fixation of single-layered gold nanoparticles: This step utilizes a connection score
1273237 五、發明說明(8) 子將金奈米粒子固定於氧化層上。以下即說明該連接分子 的製作:首先,取特定量的硫醇丙基三甲氧基矽烷(3一 mercaptopropy 1 tr imethoxysi lane,MPTMS)連接分子溶於 10¾ 升的二曱亞楓(dimethyl sulfoxide, DMS0)溶劑中, 之後,調整該溶液濃度至5mM,即完成此連接分子(MpTMS) 溶液的製備,其中該連接分子一端為矽烷基而另一端為含 硫基。以下開始進行單層金奈米粒子的固定,請參閱第3 圖’首先’將設有金奈米電極的基板浸入攝氏丨〇 〇度的連 接分子溶液中(S7),使連接分子(MPTMS)65含矽烷基的一 端與氧化層2 5形成石夕烧鍵的鍵結,之後,取出該基板以 DMS0清洗並用氮氣吹乾,接著,將基板浸入金奈米粒子溶 液中反應隔夜(S8),則連接分子(MPTMS)65含硫基的另一 端即會與金奈米粒子70產生連接,至此,即完成金奈米粒 子70藉由連接分子65固定於氧化層25上的步驟,本發明 中,固定後的金奈米粒子70係位於源極50與汲極55間的氧 化層25上’如第4圖所示。 (4 )DNA雜交及複層金奈米粒子的自組裝:首先,將 〇· 05 毫升濃度0. 01 mM 的抓取MA( capture MA,cDNA)溶液 注入ρΗ6·6濃度10mM的N- 2-羥乙基對二氮己環,N- 2 -乙磺 酸(4-(2-hydroxyethyl)_l-piperazineethanesulfonic acid,HEPES,J.T· Baker Chem· Co·)溶液中以形成一混 合溶液,該HEPES溶液的pH值係藉由濃度5mM的EDTA緩衝溶 液調整之,接著,請參閱第5圖,將固定有單層金奈米粒 子的基板浸入該混合溶液中於室溫下反應24小時(S9),以1273237 V. INSTRUCTIONS (8) The gold nanoparticles are fixed on the oxide layer. The following describes the preparation of the linker molecule: First, a specific amount of thiocaptopropy 1 tr imethoxysi lane (MPTMS) linking molecule is dissolved in 103⁄4 liter of dimethyl sulfoxide (DMS0). In the solvent, after the concentration of the solution is adjusted to 5 mM, the preparation of the linking molecule (MpTMS) solution is completed, wherein the linking molecule has a decyl group at one end and a sulfur-containing group at the other end. The following is the beginning of the fixation of the single-layered gold nanoparticles. Please refer to Figure 3 'First' to immerse the substrate with the gold nanoparticles in the solution of the coupling molecule of Celsius (S7) to make the linker (MPTMS). One end of the 65-containing alkyl group forms a bond with the oxide layer 25, and then the substrate is taken out and washed with DMS0 and dried with nitrogen. Then, the substrate is immersed in the gold nanoparticle solution to be reacted overnight (S8). Then, the other end of the linking molecule (MPTMS) 65 containing a sulfur group is linked to the gold nanoparticle 70, and thus, the step of fixing the gold nanoparticle 70 to the oxide layer 25 by the linking molecule 65 is completed. The fixed gold nanoparticle 70 is located on the oxide layer 25 between the source 50 and the drain 55 as shown in Fig. 4. (4) DNA hybridization and self-assembly of multi-layered gold nanoparticles: First, a 0.0 ml mM capture MA (collection MA, cDNA) solution was injected into a ρΗ6·6 concentration of 10 mM N-2- a solution of hydroxyethyl p-diazide, N- 2 -ethanesulfonic acid (4-(2-hydroxyethyl)_l-piperazineethanesulfonic acid, HEPES, JT·Baker Chem Co.) to form a mixed solution, the HEPES solution The pH value is adjusted by a 5 mM concentration of EDTA buffer solution. Next, referring to FIG. 5, the substrate to which the single layer of gold nanoparticles are immobilized is immersed in the mixed solution and reacted at room temperature for 24 hours (S9). Take
0522-A20466TWF(N2);david.ptd 第13頁 1273237 五、發明說明(9) ' ------- 使金奈米粒子與⑼以產生連接,續以ρΗ6·5的評^緩☆ 液(為濃度50 mM的磷酸鈉溶液與濃度〇 · 3Μ的氯化鈉溶液: 混合溶液)清洗,以去除未與金奈米粒子鍵結的cDNa分、 子,之後,再利用氮氣吹乾,即產生,如第5圖所示,抓 取DNA 75藉由其所包含的一含硫基與金奈米粒子7〇連接的 情形,上述連接過程係為一自組裝(self —assemMy)連接 過程,接著,將該基板浸入由濃度〇 · j # M的目標dna (target DNA,tDNA)溶液與〇·〇5毫升濃度1;^的探針MA (jrobe DNA, pDNA)溶液所組成的混合溶液中2小時進行雜 父反應(S10),之後,再以SPSC緩衝溶液清诜該基板以去 除基板上的殘留試劑,至此,即完成DNA的雜交工作,形 成一包含抓取DNA 75、目標DNA 80與探針DNA 85的雜交 〇“90,其中抓取〇“75的一端係與探針|)1^8 5的一端連 接’而此兩者所組成的DNA再與目標DNA 80互補形成最終 的雙版雜父D N A 9 0 ’亦請參閱第5圖,接著,將清洗完後 的基板浸入由金奈米粒子溶液與濃度〇· 3M的1^8緩衝溶液 (為ρΗ7· 0由濃度〇· 3M的氯化鈉溶液與濃度1 的填酸二氫 納/磷酸氫二鈉溶液所組成的混合溶液)所配製成的混合溶 液中(sii),以使第二層的金奈米粒子95與㈤“ 85產生連 接,續以濃度0· 3M的PBS缓衝溶液清洗基板以去除未鍵結 的金奈米粒子並利用氮氣吹乾,之後,再將基板浸入杳離 子水中2〜3秒,待取出後以氮氣吹乾並在真空條件下進〆 步烘乾,至此,即完成複層金奈米粒子的組裝,如第5圖 所示’探針DNA 85藉由其所包含的一含硫基與金奈沭粒子0522-A20466TWF(N2);david.ptd Page 13 1273237 V. Description of invention (9) ' ------- Make the connection between the gold nanoparticles and (9), and continue with the evaluation of ρΗ6·5 ☆ The liquid (a sodium phosphate solution having a concentration of 50 mM and a sodium chloride solution having a concentration of 〇·3 :: a mixed solution) is washed to remove the cDNa component which is not bonded to the gold nanoparticles, and then dried by using nitrogen gas. That is, as shown in FIG. 5, the grasping DNA 75 is connected to the gold nanoparticle 7〇 by a sulfur-containing group contained therein, and the above-mentioned joining process is a self-assembly (self-assemMy) joining process. Then, the substrate is immersed in a mixed solution of a target DNA (tDNA) solution having a concentration of 〇· j # M and a probe solution (jrobe DNA, pDNA) having a concentration of 5 ml of 〇·〇 5; The heteroactive reaction is carried out for 2 hours (S10), after which the substrate is removed by SPSC buffer solution to remove the residual reagent on the substrate, thereby completing the hybridization work of the DNA to form a DNA containing the captured DNA 75 and the target DNA 80. Hybrid with probe DNA 85 90 "90, where one end of the grab 〇 "75 is attached to the probe |) 1 ^ 8 5 The DNA consisting of the two is then complementary to the target DNA 80 to form the final double-copy parental DNA 9 0 '. See also Figure 5, and then immersing the washed substrate in a solution of the gold nanoparticles. a concentration of 〇·3M of 1 ^ 8 buffer solution (for ρ Η 7 · 0 from a concentration of 〇 · 3M sodium chloride solution and a concentration of 1 mixture of dihydrogen sodium / disodium hydrogen phosphate solution) In the mixed solution (sii), so that the second layer of gold nanoparticles 95 is connected with (5) "85, and the substrate is washed with a concentration of 0. 3M PBS buffer solution to remove unbonded gold nanoparticles and After drying with nitrogen, the substrate is immersed in helium ion water for 2 to 3 seconds, and after being taken out, it is blown dry with nitrogen and dried under vacuum, thereby completing the assembly of the multi-layered gold nanoparticles. As shown in Figure 5, 'probe DNA 85 is composed of a sulfur-containing group and a gold sulphate particle.
1273237 五、發明說明(10) 95產生連接,而上述連接 assembly)逹接過程。°利用仙一自組裝(self-析儀進行對該裝置的電性4⑸A半導體參數分 請參閱第6圖,第6圖係在宮瓜德从〇 4奈米金粒子裝置的電璧_電 μ _下刼作組裝有複層 〇. 5^0. 5 ^ # ^ ^ ^ 加而增加,僅在—Q U i 電壓值的增 電麼增加卻未見電流增加的現* ^ ^ ’而此段 應,另將電流對電壓微分,可得該的庫倫阻斷效 導電度變化,從圖上來看,π ^ ^置在此刼作條件下的 最低。 s上來看,mi伏特的區域其導電度 綜上所述,本發明的庫倫阻斷裝置具 由抓取DNA與探針DNA結合所形成的模板,使該 範圍廣泛的目標D1U,作為一有效率的⑽ ^:置可辨識 雔®全太乎粉早你盔道φ兮 、 感’則裝置’且以 又層金不未粒子作為導電薄膜,可有效降低電阻, 測靈敏度至fM的範圍。(2)本發明在室溫操作下可升座感 儉阻斷的量子效應’因此’利用該項技術可在室溫條件下 操作單電子電晶體,非常具有實用價值。 八下 而影響裝置是否在室溫下具有庫倫阻斷效應的重 素即是金奈米粒子的大小,請參閱第7圖,圖?為組 奈米金粒子的裝置在不同溫度下操作所獲得的電壓_電& 圖,圖中可看出,當於室溫操作時( 300κ,曲線a),裝= 呈現的特性為歐姆效應而非庫倫阻斷效應,須待操作'^产 降至15 0K(曲線c)或50K(曲線d)時,裝置的電壓與電淀^關^ 1 0522-A20466TWF(N2);david.ptd 第15頁 1273237 五、發明說明(11) 係才會呈現階梯式的庫倫阻斷效應,田此3知,± 1常米金 粒子的尺寸太大,製作出來的裝置,並無法在室溫條件下 具有庫倫阻斷效應。以下以載子熱能(thermal energy)與 金粒子庫倫能階(coul〇mb energy level,e2/2C)進一步說 明控制金粒子尺寸的重要性,當金粒子製作出足夠小的尺& 寸時(例如本發明10奈米以下的金粒子),可獲得相對小 電各(C ),使庫偷能階提高,雖裝置在室溫下操作,載子、 會具有較高熱能,但相較之下庫倫能階仍超過載子熱能 夕’遂使載子無法隨意在源/汲極間遷移,致形成 斷的效應’反之,若金奈米粒子太大(如14奈米的金^ 如50Κ以下,才有可能出現庫倫阻斷的量子效應。 雖然本發明已以較佳實施例揭露如上,麸^ 限定本發明,任何熟習此技藝者,在不 太ς阳^用从 和範圍内,當可作更動與潤飾,因此 /> ,精神 視後附之申請專利範圍所界定者為準。a 呆遵範圍當1273237 V. INSTRUCTIONS (10) 95 creates a connection, and the above-mentioned connection assembly) is connected. ° Using Xianyi self-assembly (self-analyzer to carry out the electrical 4 (5) A semiconductor parameter of the device, please refer to Figure 6, Figure 6 is the electricity in the Mongguade from the 4 nanometer gold particle device _ electric μ _ The lower jaw is assembled with a layer of 〇. 5^0. 5 ^ # ^ ^ ^ Add and increase, only when the voltage increase of the voltage of QU i increases, but the current increase does not see the current * ^ ^ ' and this paragraph should In addition, the current is differentiated from the voltage, and the Coulomb blocking effect conductivity change is obtained. From the figure, π ^ ^ is set to the lowest under the condition of the 。. In view of the s, the conductivity of the region of the mi volt is comprehensive. As described above, the Coulomb blocking device of the present invention has a template formed by the combination of grasping DNA and probe DNA, so that the wide range of target D1U is used as an efficient (10) ^: identifiable 雔® all too As soon as you look at the helmet, you can use the layered gold as the conductive film, which can effectively reduce the resistance and measure the sensitivity to the range of fM. (2) The invention can be raised at room temperature. The quantum effect of sensation blockage 'so' uses this technique to operate single-electron transistors at room temperature, It has practical value. The weight of the nano-particles that affects whether the device has a Coulomb blockade effect at room temperature is the size of the gold nanoparticles. Please refer to Figure 7, which is a device for group nano-particles at different temperatures. The voltage _ electric & graph obtained in the next operation, it can be seen that when operating at room temperature (300 κ, curve a), the characteristic of the package = ohmic effect instead of the Coulomb blocking effect, waiting for operation ' ^ When the output is reduced to 15 0K (curve c) or 50K (curve d), the voltage of the device and the electrodeposition ^ ^ 0522-A20466TWF (N2); david.ptd page 15 1273237 V, invention description (11) The stepwise Coulomb blocking effect will be presented, and it is known that the size of the ±1 cm gold particles is too large, and the fabricated device cannot have a Coulomb blocking effect at room temperature. (thermal energy) and gold particle coul〇mb energy level (e2/2C) further illustrate the importance of controlling the size of gold particles, when the gold particles are made small enough size & inch (for example, the present invention 10 Gold particles below the meter), you can get relatively small electricity (C), so that the library steals The energy level is improved. Although the device is operated at room temperature, the carrier will have higher thermal energy, but the Coulomb energy level still exceeds the thermal energy of the carrier, so that the carrier cannot migrate between the source and the drain. The effect of the formation of the fracture. Conversely, if the gold nanoparticles are too large (such as 14 nanometers of gold, such as 50 Å or less, the quantum effect of Coulomb blocking may occur. Although the invention has been disclosed above in the preferred embodiment, The present invention is defined by those skilled in the art, and is intended to be modified and retouched, and is therefore defined by the scope of the appended claims. a
1273237 圖式簡單說明 第1 a圖係為本發明4奈米金粒子的SpR光譜。 乐1 b圖係為1 4奈米金粒子的g p r光譜。 第2 a圖係為本發明金電極的製作流程圖。 第2b圖係為本發明金電極的圖案設計。 第3圖係為本發明固定單層金奈米粒子的流程示意 圖。 第4圖係為本發明裝置的上視圖。 第5圖係為本發明自組裝複層金奈米粒子的流程示意 圖。" 第6圖係為本發明自組裝複層金奈米粒子裝 度及電壓-電流圖。 ^ 1 第7圖係為組裝複層丨4奈米金粒子裝置在不同溫 的電壓-電流圖。 X卜 【主要元件符號說明】 20〜基板; 2 5〜氧化層; 3 0〜光阻層; 3 5〜電極圖案; 3 5 ’〜金電極; 40〜金屬鈦層; 4 5〜金膜; 50、5 0’〜源極; 55、55’〜汲極;1273237 BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1a is a SpR spectrum of 4 nanometer gold particles of the present invention. The music 1 b diagram is the g p r spectrum of the 14 nm gold particles. Figure 2a is a flow chart for the fabrication of the gold electrode of the present invention. Figure 2b is a pattern design of the gold electrode of the present invention. Fig. 3 is a schematic flow chart of the fixed single-layered gold nanoparticles of the present invention. Figure 4 is a top view of the apparatus of the present invention. Fig. 5 is a schematic flow chart showing the self-assembled multi-layered gold nanoparticles of the present invention. " Figure 6 is a self-assembled multi-layered gold nanoparticle particle size and voltage-current diagram of the present invention. ^ 1 Figure 7 is a diagram of the voltage-current diagram at different temperatures for the assembly of a stratified 丨4 nm gold particle device. X Bu [main component symbol description] 20 ~ substrate; 2 5 ~ oxide layer; 3 0 ~ photoresist layer; 3 5 ~ electrode pattern; 3 5 '~ gold electrode; 40 ~ metal titanium layer; 4 5 ~ gold film; 50, 5 0 '~ source; 55, 55' ~ bungee;
1273237 圖式簡單說明 6 0〜閘極; 6 5〜連接分子; 70、95〜金奈米粒子; 7 5〜抓取D N A ; 80〜目標DNA ; 85〜探針DNA ; Θ0〜雜交DNA ; S1〜沉積氧化層於基板上; S2〜覆蓋光阻層於氧化層上; S3〜利用電子束微影法圖案化光阻層; S 4〜蒸鐘金屬欽層於圖案化光阻層上並覆蓋該等電極 圖案; S5〜蒸鍵金膜於金屬欽層上; S 6〜利用丙酮溶液清洗基板; S7〜將基板浸入連接分子溶液中; S8〜將基板浸入金奈米粒子溶液中; S9〜將基板浸入含cDNA的混合溶液中; S1 0〜將基板浸入含tDNA與pDNA的混合溶液中進行雜 交; S1 1〜將基板浸入含金奈米粒子的混合溶液中。1273237 Schematic description of 6 0 ~ gate; 6 5 ~ connecting molecules; 70, 95 ~ gold nanoparticles; 7 5 ~ grab DNA; 80 ~ target DNA; 85 ~ probe DNA; Θ 0 ~ hybrid DNA; S1 ~ depositing an oxide layer on the substrate; S2~ covering the photoresist layer on the oxide layer; S3~ patterning the photoresist layer by electron beam lithography; S4~steaming metal layer on the patterned photoresist layer and covering The electrode pattern; S5~ steamed gold film on the metal layer; S6~ cleaning the substrate with an acetone solution; S7~ immersing the substrate in the linking molecule solution; S8~ immersing the substrate in the gold nanoparticle solution; S9~ The substrate is immersed in a mixed solution containing cDNA; S10 0~ the substrate is immersed in a mixed solution containing tDNA and pDNA for hybridization; S1 1~ the substrate is immersed in a mixed solution containing gold nanoparticles.
0522-A20466TWF(N2);david.ptd 第18頁0522-A20466TWF(N2);david.ptd第18页
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