CN1844907A - Preparation method of biosensor based on carbon nanotube - Google Patents
Preparation method of biosensor based on carbon nanotube Download PDFInfo
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- CN1844907A CN1844907A CN 200610011860 CN200610011860A CN1844907A CN 1844907 A CN1844907 A CN 1844907A CN 200610011860 CN200610011860 CN 200610011860 CN 200610011860 A CN200610011860 A CN 200610011860A CN 1844907 A CN1844907 A CN 1844907A
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Abstract
The invention relates to a method for preparing the biological sensor based on carbon nanometer tube, which comprises: processing stack function between the nitrogen aromatic ring of single-chain DNA alkali group and the pi key of carbon six-membered ring of carbon nanometer tube wall, and connecting the spiral compound structure formed by the single-chain DNA and the carbon nanometer tube on the metallic electrode to form a biological sensor. The inventive biological sensor can realize the sequence recognize of DNA, to check the complete complementary or un-complementary single-chain DNA. The invention has simple process, stable property and high sensitivity.
Description
Technical field
The invention belongs to the development field of biology sensor, be specifically related to a kind of preparation method of the biology sensor based on carbon nano-tube.
Background technology
Nanometer electronic device is one of the most popular research direction in present nanosecond science and technology field.Nanometer electronic device and circuit thereof have successfully been developed in recent years in succession based on monodimension nanometer material (carbon nano-tube, nano wire etc.), although nanometer electronic device is studied prematurity still, device and integratedly still have a very long segment distance apart from practicability, but the preparation of single nanometer electronic device is not difficult, stable performance, favorable repeatability, and because responses such as its yardstick is little, electricity to external world, light, magnetic are responsive, so have broad prospect of application in highly sensitive field of biosensors.The research group of the C.M.Lieber of Harvard University and the H.J.Dai of Stanford University etc. has carried out ground-breaking research work in succession in this respect and has obtained impressive progress, they have realized sensing (F.Patolsky, the G.F.Zheng ﹠amp of biomacromolecule (protein, virus etc.) with silicon nanowires or carbon nano-tube; O.Hayden et al., PNAS, vol.101,14017-14022,2004; R.J.Chen, S.Bangsaruntip ﹠amp; K.A.Drouvalakis et al., PNAS, vol.100,4984-4989,2003).Also there is research group to attempt utilizing silicon nanowires to detect dna sequence dna (Z.Li, Y.Chen ﹠amp; X.Li et al., Nano Lett., Vol.4, NO.2,245-247,2004), the silicon nanowires device is exposed in the argon gas atmosphere that contains MPTMS (3-mercaptopropyltrimethoxysilane), treat on surface of silicon nanowires, to modify one deck mercaptan after a period of time, if 5 ' the terminal modified acrylic phosphoramidite at single stranded DNA, this single stranded DNA can be connected on the silicon nanowires, if contain single stranded DNA with the single stranded DNA complementation of surface of silicon nanowires in the detected solution, then the base complementrity pairing process electricity that can obviously change the silicon nanowires device is led; If the pairing DNA that is non-complementary, then to lead variation very little for the electricity of device, thereby realize the detection to particular sequence DNA.But in order to make DNA be adsorbed on surface of silicon nanowires, must modify mercaptan and strand nucleotide in advance in this invention, complex process, and careless manipulation is easily introduced foreign matter and is influenced accuracy of detection.
Summary of the invention
At the problems referred to above, the present invention selects carbon nano-tube for use, and the method for a kind of preparation based on the nano biological sensor of carbon nano-tube is provided.
A kind of preparation method of the nano biological sensor based on carbon nano-tube, step comprises:
1) metal electrode of preparation micron or nanoscale;
2) utilize between the π key in the carbon hexatomic ring of aromatic ring nitrogenous in the single-chain DNA base and carbon nano-tube wall the stacking effect takes place, make the spiral composite structure of carbon nano-tube and single stranded DNA;
3) the spiral composite structure with carbon nano-tube and single stranded DNA is overlapped on metal electrode to last formation nano biological sensor.
Make metal electrode by photoetching in the micro-processing technology and lift-off technology, wherein the spacing of comparative electrode is controlled at 350nm～2 μ m, and the spacing of adjacent electrode is in the 250-500nm scope.
The sequence of single stranded DNA is known, and length range is tens to 100 base-pairs.
The solution of carbon nanotubes and single stranded DNA is mixed and carry out sonicated, form the screw type composite structure of carbon nano-tube and single stranded DNA.
Utilize the method for physics or chemistry to be overlapped on metal electrode the screw type composite structure of the carbon nano-tube that obtained and single stranded DNA, obtain to detect the senser element of dna sequence dna last.
The present invention has following characteristics:
Carbon nano-tube electricity transport property is very responsive to its surface structure, in the spiral complex structural device of carbon nano-tube and single stranded DNA, if absorption, pairing and its single stranded DNA complementation or non-complementary DNA, can make this device present different electrology characteristics, promptly can realize detection particular sequence DNA by the variation of monitoring its electrology characteristic.
Advantage of the present invention and technique effect
Existing DNA sensor needs that in advance nano structural material and single stranded DNA are carried out chemical modification respectively and both could be linked together, and complex process, cost height are not easy to operate.And the present invention only need and carry out sonicated with carbon nano-tube and the mixing of single stranded DNA solution, can obtain the spiral composite structure of carbon nano-tube and DNA, simple to operate, cost is low, be easy to produce in batches, if introduce to the market, might be as disposable use senser element.
Secondly, compare with the DNA sensor of report, the present invention can improve sensitivity.In the DNA sensor that background technology is chatted, single stranded DNA is to be connected on carbon nano-tube or the silicon nanowires, and links to each other by the third material between the two.And the single stranded DNA spiral directly is wrapped in carbon nano tube surface among the present invention, and its electrology characteristic changes will be responsive more, thereby improve sensitivity.
The present invention has realized the detection of particular sequence single stranded DNA by the spiral composite structure of carbon nano-tube and single stranded DNA.Compare with the various DNA sensors of being reported before, the present invention has that manufacture craft is simple, device architecture and advantages such as stable performance, sensitivity height.
Description of drawings
Fig. 1 (a) is the structural representation of biology sensor of the present invention;
Fig. 1 (b) is the enlarged drawing of red frame among Fig. 1 (a);
Fig. 2 is the stereoscan photograph (wherein comprising some to electrode) of biological senser element.
Embodiment
1, electrode design and preparation
The metal electrode of design micro-meter scale, designing its width is 2 μ m, and the spacing of comparative electrode is 2 μ m, and the spacing of adjacent electrode is about 500nm.The silicon dioxide that thermal oxide growth 300nm is thick on the heavily doped silicon substrate of P type utilizes photoetching and stripping technology to prepare metal electrode as insulation course, and its process is: whirl coating photoetching, exposure and development; Sputtering sedimentation metal then removes photoresist and peels off, and can obtain metal electrode, and electrode material is Ti/Au (10nm/100nm).
2, form the spiral composite structure of carbon nano-tube and single stranded DNA
Single stranded DNA is dissolved in (resistivity is 18M Ω cm) in the deionized water, and concentration is 20 μ M; Carbon nano-tube is dissolved in the dimethyl formamide (DMF), and its concentration is 0.1mg/ml.Carbon nano-tube solution and single stranded DNA solution are mixed with 4: 1 ratio, and the sequence of single stranded DNA is known, and length range is tens to 100 base-pairs.Mixed solution at room temperature ultrasonic 150 minutes (ultrasonic power is 200W) carries out sonicated, can make single stranded DNA be wrapped in the surface of carbon nano-tube, forms the screw type composite structure of carbon nano-tube and single stranded DNA.
3, the carbon nano-tube of acquisition screw type composite structure and single stranded DNA are overlapped on form nanometer electronic device on the metal electrode;
The drips of solution of spiral composite structure that will contain carbon nano-tube and single stranded DNA is on electrode, by applying voltage (0.5-5V at the metal electrode two ends
Pp), the alternating current of frequency (1-10MHz), utilize dielectrophoresis force directly carbon nano-tube to be overlapped on the electrode, make required senser element.
4, identification particular sequence single stranded DNA to be detected
(solvent is a deionized water will to contain the solution of single stranded DNA to be detected, resistivity is 18M Ω cm) drop on the above-mentioned device, and the variation of synchronous detection device electrology characteristic, if contained single stranded DNA and the single stranded DNA complementation in this composite structure in the detected solution, then it will cause the variation of device electrology characteristic; Otherwise electric properties of devices does not have obvious variation, has promptly realized the detection to particular sequence DNA in this way.
Claims (4)
1, a kind of preparation method of the nano biological sensor based on carbon nano-tube, step comprises:
(1) metal electrode of preparation micron or nanoscale;
(2) utilize between the π key in the carbon hexatomic ring of aromatic ring nitrogenous in the single-chain DNA base and carbon nano-tube wall the stacking effect takes place, make the spiral composite structure of carbon nano-tube and single stranded DNA;
(3) the spiral composite structure with carbon nano-tube and single stranded DNA utilizes the method for physics or chemistry to be overlapped on metal electrode to last formation nano biological sensor.
2, the preparation method of the nano biological sensor based on carbon nano-tube as claimed in claim 1, it is characterized in that: adopt photoetching and lift-off technology in the micro-processing technology to make metal electrode, wherein the spacing of positive and negative electrode is controlled at 350nm～2 μ m, and the spacing of adjacent electrode is in the 250nm-500nm scope.
3, the preparation method of the nano biological sensor based on carbon nano-tube as claimed in claim 1 or 2 is characterized in that: the solution that carbon nano-tube and single stranded DNA are mixed carries out sonicated, forms the screw type composite structure of carbon nano-tube and single stranded DNA.
4, the preparation method of the nano biological sensor based on carbon nano-tube as claimed in claim 1 or 2, it is characterized in that:, utilize dielectrophoresis force that the spiral composite structure of carbon nano-tube and single stranded DNA is overlapped on metal electrode to last by apply the alternating current of certain frequency and voltage at the metal electrode two ends.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101271079B (en) * | 2008-05-07 | 2010-12-08 | 天津大学 | Glass carbon electrode decorated by carbon nano tube-DNA complex and its production method and application |
| CN102317776A (en) * | 2008-08-22 | 2012-01-11 | 成均馆大学产业协力团 | Utilize linking group and spacer groups to improve carbon nanotube-based biology sensor sensitivity of method |
| US8106428B2 (en) | 2009-03-03 | 2012-01-31 | Board Of Regents, The University Of Texas System | Nano-scale bridge biosensors |
| CN103630571A (en) * | 2013-09-12 | 2014-03-12 | 中国科学院电子学研究所 | Micro-nano array sensor and preparation method thereof |
| CN104409558A (en) * | 2014-12-21 | 2015-03-11 | 浙江理工大学 | Manufacturing method of nano-photoelectric device based on CdS (Cadmium Sulfide) nano-rods |
| CN106404840A (en) * | 2016-08-24 | 2017-02-15 | 北京大学 | Method for realizing surface modification of nanowire biosensor |
| CN111175347A (en) * | 2019-12-26 | 2020-05-19 | 清华大学 | Preparation method and application of nanowire biosensor |
Family Cites Families (6)
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| KR100455284B1 (en) * | 2001-08-14 | 2004-11-12 | 삼성전자주식회사 | High-throughput sensor for detecting biomolecules using carbon nanotubes |
| US20030148289A1 (en) * | 2002-02-04 | 2003-08-07 | Intel Corporation | Modified carbon nanotubes as molecular labels with application to DNA sequencing |
| CN1187611C (en) * | 2002-04-28 | 2005-02-02 | 武汉大学 | Ultratrace DNA detecting method by means of nano microsphere amplificaltion technology and piezoelectric DNA biosensor |
| US7361821B2 (en) * | 2002-09-20 | 2008-04-22 | Intel Corporation | Controlled alignment of nanobarcodes encoding specific information for scanning probe microscopy (SPM) reading |
| CN1215327C (en) * | 2003-09-17 | 2005-08-17 | 中国科学院长春应用化学研究所 | Preparation method of deoxyribonucleic acid electrochemical nanometer sensor |
| US7687234B2 (en) * | 2003-12-15 | 2010-03-30 | Geneohm Sciences, Inc. | Carbon electrode surface for attachment of DNA and protein molecules |
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2006
- 2006-05-09 CN CNB2006100118600A patent/CN100412537C/en active Active
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101271079B (en) * | 2008-05-07 | 2010-12-08 | 天津大学 | Glass carbon electrode decorated by carbon nano tube-DNA complex and its production method and application |
| CN102317776A (en) * | 2008-08-22 | 2012-01-11 | 成均馆大学产业协力团 | Utilize linking group and spacer groups to improve carbon nanotube-based biology sensor sensitivity of method |
| US8106428B2 (en) | 2009-03-03 | 2012-01-31 | Board Of Regents, The University Of Texas System | Nano-scale bridge biosensors |
| CN103630571A (en) * | 2013-09-12 | 2014-03-12 | 中国科学院电子学研究所 | Micro-nano array sensor and preparation method thereof |
| CN103630571B (en) * | 2013-09-12 | 2015-08-19 | 中国科学院电子学研究所 | A kind of micro-nano array sensor and preparation method thereof |
| CN104409558A (en) * | 2014-12-21 | 2015-03-11 | 浙江理工大学 | Manufacturing method of nano-photoelectric device based on CdS (Cadmium Sulfide) nano-rods |
| CN106404840A (en) * | 2016-08-24 | 2017-02-15 | 北京大学 | Method for realizing surface modification of nanowire biosensor |
| CN111175347A (en) * | 2019-12-26 | 2020-05-19 | 清华大学 | Preparation method and application of nanowire biosensor |
| CN111175347B (en) * | 2019-12-26 | 2020-12-29 | 清华大学 | Preparation method and application of nanowire biosensor |
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| CN100412537C (en) | 2008-08-20 |
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