WO2005054869A1 - Biosensor comprising zinc oxide-based nanorod and preparation thereof - Google Patents

Biosensor comprising zinc oxide-based nanorod and preparation thereof Download PDF

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Publication number
WO2005054869A1
WO2005054869A1 PCT/KR2004/003197 KR2004003197W WO2005054869A1 WO 2005054869 A1 WO2005054869 A1 WO 2005054869A1 KR 2004003197 W KR2004003197 W KR 2004003197W WO 2005054869 A1 WO2005054869 A1 WO 2005054869A1
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nanorod
biosensor
zno
group
substrate
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PCT/KR2004/003197
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French (fr)
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Gyu-Chul Yi
Jin Suk Kim
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Postech Foundation
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • C12Q1/6825—Nucleic acid detection involving sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
    • G01N27/04—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance
    • G01N27/12—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluid; of a solid body in dependence upon reaction with a fluid, for detecting components in the fluid
    • G01N27/125—Composition of the body, e.g. the composition of its sensitive layer
    • G01N27/127—Composition of the body, e.g. the composition of its sensitive layer comprising nanoparticles
    • 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
    • G01N27/4146—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS involving nanosized elements, e.g. nanotubes, nanowires
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/553—Metal or metal coated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/563—Immunoassay; Biospecific binding assay; Materials therefor involving antibody fragments

Definitions

  • the present invention relates to a novel biosensor comprising a ZnO- based nanorod sensor and a process for the preparation thereof.
  • One-dimensional nanostructures such as nanotubes, nanowires and nanorods have attracted immense attention because of their potential use as building blocks in fabricating nanoscale devices or sensors.
  • chemical sensors for detecting toxic gases such as N0 2 and NH 3 have been developed by H. Dai et al. who exploited a single-walled carbon nanotube (see [H. Dai et al., Science 287, (2000) 622]); and a biosensor comprising a carbon nanotube (CNT) that can detect biotin-streptavidin binding has been developed by Alexander Star et al. (see [Alexander Star et al., Nano letters, 2003, vol. 3, 459]).
  • a biosensor comprising an oxide semiconductor nanostructure which is chemically stable and has a high specific surface area, capable of detecting clinically important species with a high sensitivity and reproducibility. It is another object of the present invention to provide a method for preparing such a biosensor.
  • a biosensor comprising a first electrode, a sensing layer comprising a ZnO-based nanorod one end of which is attached to the first electrode, and a second electrode to which the other end of the ZnO-based nanorod is attached.
  • a process for preparing said biosensor which comprises the steps of horizontally or vertically disposing the ZnO-based nanorod on a non- conductive or conductive substrate, and forming an electrode at the tip portion of the nanorod
  • Figs, la and lb a schematic diagram and a scanning electron microscope scan of the biosensor obtained in Example 1 of the present invention, respectively, which comprises a ZnO nanorod horizontally disposed on a substrate
  • Fig. 2a a schematic diagram of the scanning electron microscope scan of the biosensor obtained in Example 2 of the present invention, which comprises a ZnO nanorod vertically disposed on a substrate
  • Fig. 2b a scanning electron microscope scan thereof
  • FIG. 3 a schematic diagram of the biosensor obtained in Example 3 of the present invention, which comprises a PEG-coated ZnO nanorod;
  • Figs. 4a and 4b the changes in the electrical characteristic of the biosensor obtained in Example 3 of the present invention for detecting the biotin-streptavidin and biotinPEG-streptavidin bindings;
  • Fig. 5 the change in the electrical characteristic of the biosensor obtained in Example 1 of the present invention for detecting low-density lipoprotein (LDL);
  • Fig. 6 the change in the electrical characteristic of the biosensor obtained in Example 2 of the present invention for detecting low-density lipoprotein (LDL).
  • the inventive biosensor is characterized in that it comprises a ZnO- based nanorod in the sensing layer.
  • the ZnO-based nanorod may be horizontally disposed on a non-conductive substrate between two electrodes or vertically disposed on a conductive substrate, the tip thereof being attached to a second electrode.
  • a zinc oxide (ZnO), nanorod is an efficient semiconductor sensing material because of its direct transition band structure (3.4 eV), a high specific surface area and chemical stability, and the fact that its band-gap and electrical conductivity can be easily controlled by doping or coating the nanorod with a heteromaterial such as Cd, Mg, Al, Ga, etc.
  • the ZnO-based nanorod of the inventive sensor may be a ZnO nanorod; a ZnO nanorod doped with at least one heteromaterial selected from the group consisting of Mg, Cd, Ti, Li, Cu, Al, Ni, Y, Ag, Mn, V, Fe, La, Ta, Nb, Ga, In, S, Se, P, As, Co, Cr, B, N, Sb and H; or a core-shell ZnO nanorod having a shell coating of a heteromaterial such as GaN, A1N, InN, GaAg, InP, GaP and a composite thereof.
  • a heteromaterial such as GaN, A1N, InN, GaAg, InP, GaP and a composite thereof.
  • the ZnO-based nanorod may be further coated with a polymer selected from the group consisting of polyethylene glycol (PEG), polyethylene imine (PEI), PEG modified with polylactic acid (PLA) or others.
  • the nanorod may further be coated with an organic material such as polydiallyldimethylammonium chloride, polysodium 4-styrenesulfonate and diazo resin, which may enhance the adsorption of a target biomolecule to the nanorod.
  • the ZnO nanorod of the inventive biosensor may be formed by a metal organic chemical vapor deposition (MOCVD) method, comprising the steps of bringing the vapors of a Zn-metallorganic compound and an oxygen- containing compound into contact with a non-conductive substrate such as a glass, pyrex and sapphire plate or a conductive substrate such as a metal, silicone (Si), and a conductive oxide and polymer plate, at room temperature to 800 ° C , preferably 400 to 700 ° C , under a pressure in the range of 0.1 to lO torr.
  • MOCVD metal organic chemical vapor deposition
  • the heteromaterial-doped or -coated ZnO nanorod may be formed by introducing the vapor of a compound containing the heteromaterial at the time of introducing the reactant vapors or after the formation of the ZnO nanorod.
  • Exemplary Zn-containing metal organic compounds that can be used as precursors for zinc oxide in the present invention include dimethylzinc [Zn(CH 3 ) 2 ], diethylzinc [Zn(C 2 H 5 ) 2 ], zinc acetate [Zn(OOCCH 3 ) 2 • H 2 0], zinc acetate anhydride [Zn(OOCCH 3 ) 2 ], and zinc acetyl acetonate [Zn(C 5 H 7 0 2 ) 2 ]; and examples of the oxygen-containing compounds are 0 2 , 0 3 , N0 2 , H 2 0 (vapor), C0 2 and C 4 H 8 0.
  • the heteromaterial- containing metal organic compound that can be used as a precursor for doping or coating the nanorod may be a conventional metal organic compound used in a metal organic chemical deposition method.
  • the diameter, length and density of ZnO-based nanorods formed on a substrate can be controlled by varying the reaction conditions such as the amount of gaseous reactants introduced into a reaction chamber, deposition temperature and pressure, etc., during their growth.
  • the nanorod of the inventive sensor preferably has a diameter in the range of 6 to 200 nm and a length in the range of 100 nm to 10 ⁇ .
  • the ZnO-based nanorod of the inventive sensor is free from any contaminants derived from catalytical materials since it is formed by direct growth of the nanorod without using a catalyst.
  • the inventive biosensor may be prepared, e.g., by growing ZnO- based nanorod on a substrate, separating the nanorod from the substrate, suspending the separated nanorod in an organic solvent, depositing the suspension such that the nanorod is disposed on a non-conductive substrate such as a Si0 2 /Si, glass, quartz, pyrex, sapphire or plastic plate, and then forming source and drain ohmic electrodes on both ends of the nanorod, e.g., using a thermal or electron beam evaporation technique, as shown in Fig. la.
  • the inventive biosensor may be fabricated by forming an electrode plate that covers the tip portion of the array of ZnO-based nanorods epitaxially grown on a conductive substrate, as shown in Fig. 2a.
  • the surface coating process of the ZnO-based nanorod may be conducted by immersing the biosensor in a solution of a desired polymer or organic material for 12 to 14 hours, to obtain e.g., a biosensor as shown in Fig.3.
  • the inventive biosensor can detect an antigen-antibody binding (e.g., the binding of biotin or modified biotin to streptavidin or modified streptavidin); a biomolecule such as low-density lipoprotein (LDL), polynucleotide and polypeptide; and interactions thereof, with a high sensitivity and reproducibility, and thus it can be advantageously used in biotechnology such as gene analysis, disease diagnosis and the like.
  • an antigen-antibody binding e.g., the binding of biotin or modified biotin to streptavidin or modified streptavidin
  • a biomolecule such as low-density lipoprotein (LDL), polynucleotide and polypeptide
  • Example 1 Fabrication of biosensor comprising one ZnO nanorod horizontally disposed on a substrate ZnO nanorods were grown on a Si substrate by injecting gaseous
  • an Au (500 A)/ Ti (300 A) ohmic electrodes were deposited on the both ends of the ZnO nanorod by an electron beam evaporation technique and heated to about 300 ° C for 1 minute, to obtain a biosensor comprising a ZnO nanorod horizontally disposed on a substrate as shown in Fig. la.
  • a scanning electron microscope (SEM) photograph of the biosensor thus obtained is shown in Fig. lb, which reveals that a single ZnO nanorod having a 50 nm diameter and 3 ⁇ m length is horizontally disposed between the Au/Ti source and drain electrodes.
  • Example 2 Fabrication of biosensor comprising ZnO nanorods vertically disposed on a substrate
  • ZnO nanorods were epitaxially grown on a Si substrate by injecting gaseous Zn(CH 3 ) 2 and 0 2 through separate inlets at flow rates of 3 seem and 20 seem, respectively, with an argon (Ar) carrier gas and allowing the vapors to react for about 1 hour.
  • the reactor pressure and temperature were maintained at 1 torr and 500 ° C, respectively, during the ZnO nanorod growth.
  • an Au (500 A) /Ti (300 A) ohmic electrode was formed such that it forms a horizontal plate covering the tip portion of the ZnO nanorods by an electron beam evaporation technique and heated to about 300 ° C for 1 minute, to obtain a biosensor comprising ZnO nanorods vertically disposed on the substrate as shown in Fig. 2a.
  • a scanning electron microscope (SEM) photograph of the biosensor thus obtained is shown in Fig. 2b, which reveal ZnO nanorods each having a 50 nm diameter and 3 ⁇ m length are uniformly and vertically grown on the surface of the substrate.
  • Test Example 1 Biotin-streptavidin binding detection
  • Example 2 Two biosensors obtained in Example 1 were submerged in a solution of 0.0337 g of PEG in 2250 ⁇ i of deionized water for about 20 hours, to coat the surface of the ZnO nanorod with PEG, as shown in Fig. 3. Then, 5 ⁇ i of I ⁇ M biotin (an antigen) or 1 ⁇ M PEG-modif ⁇ ed biotin was dropped on the sensor to allow the ZnO nanorod to adsorb biotin or biotinPEG, and the current (I) changes with respect to the gate voltage (V) were measured. The results are shown in Figs. 4a and 4b, respectively.
  • the inventive biosensor comprising one ZnO nanorod horizontally disposed on a substrate is capable of detecting LDL with a high sensitivity.
  • Test Example 3 LDL detection The procedure of Test Example 2 was repeated except that the biosensor obtained in Example 2 was used instead of the biosensor obtained in Example 1, to investigate its characteristics for sensing LDL.
  • the result represented by Fig. 6 demonstrates that the inventive biosensor comprising an array of ZnO nanorods disposed between a conductive substrate and an electrode plate formed on the tips thereof is also suitable for detecting LDL with a high sensitivity.

Abstract

A biosensor comprising a ZnO-based nanorod grown by metal organic deposition (MOCVD) is capable of detecting antigen/antibody bindings, biomolecules and others with a high sensitivity and reproducibility, and thus it can be advantageously used in gene analysis, disease diagnosis, etc.

Description

BIOSENSOR COMPRISING ZINC OXIDE-BASED NANOROD AND PREPARATION THEREOF
Field of the Invention
The present invention relates to a novel biosensor comprising a ZnO- based nanorod sensor and a process for the preparation thereof.
Background of the Invention
One-dimensional nanostructures such as nanotubes, nanowires and nanorods have attracted immense attention because of their potential use as building blocks in fabricating nanoscale devices or sensors. For example, chemical sensors for detecting toxic gases such as N02 and NH3 have been developed by H. Dai et al. who exploited a single-walled carbon nanotube (see [H. Dai et al., Science 287, (2000) 622]); and a biosensor comprising a carbon nanotube (CNT) that can detect biotin-streptavidin binding has been developed by Alexander Star et al. (see [Alexander Star et al., Nano letters, 2003, vol. 3, 459]). However, the application of a CNT to sensors is hampered by the difficulty of controlling its electrical conductivity. There has also been developed a nanosensor comprising a semiconductor silicone nanowire, which can detect various biomolecules (see [H. Park, CM. Lieber et al., Science 293, (2001) 1289]). Such a biosensor, however, exhibits a low sensitivity due to the insulating oxide layer formed on the surface of the silicone nanowire. Semiconductor nanowires, on the other hand, are free from such problems associated with the conventional sensors. Summary of the Invention
Accordingly, it is a primary object of the present invention to provide a biosensor comprising an oxide semiconductor nanostructure which is chemically stable and has a high specific surface area, capable of detecting clinically important species with a high sensitivity and reproducibility. It is another object of the present invention to provide a method for preparing such a biosensor. In accordance with one aspect of the present invention, there is provided a biosensor comprising a first electrode, a sensing layer comprising a ZnO-based nanorod one end of which is attached to the first electrode, and a second electrode to which the other end of the ZnO-based nanorod is attached. In accordance with another aspect of the present invention, there is provided a process for preparing said biosensor, which comprises the steps of horizontally or vertically disposing the ZnO-based nanorod on a non- conductive or conductive substrate, and forming an electrode at the tip portion of the nanorod
Brief Description of the Drawings
The above and other objects and features of the present invention will become apparent from the following description of the invention, when taken in conjunction with the accompanying drawings, which respectively show: Figs, la and lb: a schematic diagram and a scanning electron microscope scan of the biosensor obtained in Example 1 of the present invention, respectively, which comprises a ZnO nanorod horizontally disposed on a substrate; Fig. 2a: a schematic diagram of the scanning electron microscope scan of the biosensor obtained in Example 2 of the present invention, which comprises a ZnO nanorod vertically disposed on a substrate, and Fig. 2b, a scanning electron microscope scan thereof; Fig. 3 : a schematic diagram of the biosensor obtained in Example 3 of the present invention, which comprises a PEG-coated ZnO nanorod; Figs. 4a and 4b: the changes in the electrical characteristic of the biosensor obtained in Example 3 of the present invention for detecting the biotin-streptavidin and biotinPEG-streptavidin bindings; Fig. 5: the change in the electrical characteristic of the biosensor obtained in Example 1 of the present invention for detecting low-density lipoprotein (LDL); and Fig. 6: the change in the electrical characteristic of the biosensor obtained in Example 2 of the present invention for detecting low-density lipoprotein (LDL).
Detailed Description of the Invention The inventive biosensor is characterized in that it comprises a ZnO- based nanorod in the sensing layer. In the inventive biosensor, the ZnO-based nanorod may be horizontally disposed on a non-conductive substrate between two electrodes or vertically disposed on a conductive substrate, the tip thereof being attached to a second electrode. A zinc oxide (ZnO), nanorod is an efficient semiconductor sensing material because of its direct transition band structure (3.4 eV), a high specific surface area and chemical stability, and the fact that its band-gap and electrical conductivity can be easily controlled by doping or coating the nanorod with a heteromaterial such as Cd, Mg, Al, Ga, etc. The ZnO-based nanorod of the inventive sensor may be a ZnO nanorod; a ZnO nanorod doped with at least one heteromaterial selected from the group consisting of Mg, Cd, Ti, Li, Cu, Al, Ni, Y, Ag, Mn, V, Fe, La, Ta, Nb, Ga, In, S, Se, P, As, Co, Cr, B, N, Sb and H; or a core-shell ZnO nanorod having a shell coating of a heteromaterial such as GaN, A1N, InN, GaAg, InP, GaP and a composite thereof. Also, the ZnO-based nanorod may be further coated with a polymer selected from the group consisting of polyethylene glycol (PEG), polyethylene imine (PEI), PEG modified with polylactic acid (PLA) or others. The nanorod may further be coated with an organic material such as polydiallyldimethylammonium chloride, polysodium 4-styrenesulfonate and diazo resin, which may enhance the adsorption of a target biomolecule to the nanorod. The ZnO nanorod of the inventive biosensor may be formed by a metal organic chemical vapor deposition (MOCVD) method, comprising the steps of bringing the vapors of a Zn-metallorganic compound and an oxygen- containing compound into contact with a non-conductive substrate such as a glass, pyrex and sapphire plate or a conductive substrate such as a metal, silicone (Si), and a conductive oxide and polymer plate, at room temperature to 800 °C , preferably 400 to 700 °C , under a pressure in the range of 0.1 to lO torr. Further, the heteromaterial-doped or -coated ZnO nanorod may be formed by introducing the vapor of a compound containing the heteromaterial at the time of introducing the reactant vapors or after the formation of the ZnO nanorod. Exemplary Zn-containing metal organic compounds that can be used as precursors for zinc oxide in the present invention include dimethylzinc [Zn(CH3)2], diethylzinc [Zn(C2H5)2], zinc acetate [Zn(OOCCH3)2 • H20], zinc acetate anhydride [Zn(OOCCH3)2], and zinc acetyl acetonate [Zn(C5H702)2]; and examples of the oxygen-containing compounds are 02, 03, N02, H20 (vapor), C02 and C4H80. Also, the heteromaterial- containing metal organic compound that can be used as a precursor for doping or coating the nanorod may be a conventional metal organic compound used in a metal organic chemical deposition method. The diameter, length and density of ZnO-based nanorods formed on a substrate can be controlled by varying the reaction conditions such as the amount of gaseous reactants introduced into a reaction chamber, deposition temperature and pressure, etc., during their growth. The nanorod of the inventive sensor preferably has a diameter in the range of 6 to 200 nm and a length in the range of 100 nm to 10 μ . The ZnO-based nanorod of the inventive sensor is free from any contaminants derived from catalytical materials since it is formed by direct growth of the nanorod without using a catalyst. The inventive biosensor may be prepared, e.g., by growing ZnO- based nanorod on a substrate, separating the nanorod from the substrate, suspending the separated nanorod in an organic solvent, depositing the suspension such that the nanorod is disposed on a non-conductive substrate such as a Si02/Si, glass, quartz, pyrex, sapphire or plastic plate, and then forming source and drain ohmic electrodes on both ends of the nanorod, e.g., using a thermal or electron beam evaporation technique, as shown in Fig. la. Alternatively, the inventive biosensor may be fabricated by forming an electrode plate that covers the tip portion of the array of ZnO-based nanorods epitaxially grown on a conductive substrate, as shown in Fig. 2a. The surface coating process of the ZnO-based nanorod may be conducted by immersing the biosensor in a solution of a desired polymer or organic material for 12 to 14 hours, to obtain e.g., a biosensor as shown in Fig.3. The inventive biosensor can detect an antigen-antibody binding (e.g., the binding of biotin or modified biotin to streptavidin or modified streptavidin); a biomolecule such as low-density lipoprotein (LDL), polynucleotide and polypeptide; and interactions thereof, with a high sensitivity and reproducibility, and thus it can be advantageously used in biotechnology such as gene analysis, disease diagnosis and the like. The present invention will be described in further detail by the following Examples, which are, however, not intended to limit the scopes of the present invention.
Example 1 : Fabrication of biosensor comprising one ZnO nanorod horizontally disposed on a substrate ZnO nanorods were grown on a Si substrate by injecting gaseous
Zn(CH3)2 and 02 through separate inlets at flow rates of 3 seem and 20 seem, respectively, with an argon (Ar) carrier gas and allowing the vapors to react for about 1 hour. The reactor pressure and temperature were maintained at 1 torr and 500 °C , respectively, during the ZnO nanorod growth. Subsequently, the grown ZnO nanorod was separated from the substrate by scratching with a knife, mixed with ethanol, placed on a Si02/Si substrate, and then the nanorod was disposed on a preset position of the substrate using an electron microscope. Then, an Au (500 A)/ Ti (300 A) ohmic electrodes were deposited on the both ends of the ZnO nanorod by an electron beam evaporation technique and heated to about 300 °C for 1 minute, to obtain a biosensor comprising a ZnO nanorod horizontally disposed on a substrate as shown in Fig. la. A scanning electron microscope (SEM) photograph of the biosensor thus obtained is shown in Fig. lb, which reveals that a single ZnO nanorod having a 50 nm diameter and 3 μm length is horizontally disposed between the Au/Ti source and drain electrodes.
Example 2: Fabrication of biosensor comprising ZnO nanorods vertically disposed on a substrate
ZnO nanorods were epitaxially grown on a Si substrate by injecting gaseous Zn(CH3)2 and 02 through separate inlets at flow rates of 3 seem and 20 seem, respectively, with an argon (Ar) carrier gas and allowing the vapors to react for about 1 hour. The reactor pressure and temperature were maintained at 1 torr and 500 °C, respectively, during the ZnO nanorod growth. Then, an Au (500 A) /Ti (300 A) ohmic electrode was formed such that it forms a horizontal plate covering the tip portion of the ZnO nanorods by an electron beam evaporation technique and heated to about 300 °C for 1 minute, to obtain a biosensor comprising ZnO nanorods vertically disposed on the substrate as shown in Fig. 2a. A scanning electron microscope (SEM) photograph of the biosensor thus obtained is shown in Fig. 2b, which reveal ZnO nanorods each having a 50 nm diameter and 3 μm length are uniformly and vertically grown on the surface of the substrate. Test Example 1 :Biotin-streptavidin binding detection
Two biosensors obtained in Example 1 were submerged in a solution of 0.0337 g of PEG in 2250 μi of deionized water for about 20 hours, to coat the surface of the ZnO nanorod with PEG, as shown in Fig. 3. Then, 5 μi of I μM biotin (an antigen) or 1 μM PEG-modifϊed biotin was dropped on the sensor to allow the ZnO nanorod to adsorb biotin or biotinPEG, and the current (I) changes with respect to the gate voltage (V) were measured. The results are shown in Figs. 4a and 4b, respectively. Subsequently, 5 μi of 200 μM streptavidin (an antibody), was dropped on the sensor thus treated with biotin or biotinPEG, and the current (I) changes with respect to the gate voltage (V) were measured. The results shown in Figs. 4a and 4b illustrate that the current is almost constant with respect to the increase of the gate voltage before the streptavidin exposure, but spectacularly increases when exposed to streptavidin. The above results suggest that the inventive biosensor comprising one ZnO-nanorod horizontally disposed on a substrate can detect the biotin- streptavidin binding with a high sensitivity.
Test Example 2: LDL detection
1 ml of LDL (low density lipoprotein) was dissolved in a mixture of 0.5 ml of 0.15 M NaCl and 0.5 ml of 0.01% EDTA, and freeze-dried under a reduced pressure at pH 7.4. 0.004 mg of the resulting residue was dissolved in 1 ml of ethanol, 5 μi of which was dropped on the sensor obtained in Example 1, and the current (I) change with respect to the gate voltage (V) was measured before and after exposure to LDL. The result shown in Fig. 5 illustrates that the current with respect to the increase of the gate voltage is significantly suppressed when the LDL solution is applied onto the sensor. Thus, the inventive biosensor comprising one ZnO nanorod horizontally disposed on a substrate is capable of detecting LDL with a high sensitivity.
Test Example 3: LDL detection The procedure of Test Example 2 was repeated except that the biosensor obtained in Example 2 was used instead of the biosensor obtained in Example 1, to investigate its characteristics for sensing LDL. The result represented by Fig. 6 demonstrates that the inventive biosensor comprising an array of ZnO nanorods disposed between a conductive substrate and an electrode plate formed on the tips thereof is also suitable for detecting LDL with a high sensitivity. While the embodiments of the subject invention have been described and illustrated, it is obvious that various changes and modifications can be made therein without departing from the spirit of the present invention which should be limited only by the scope of the appended claims.

Claims

What is claimed is:
1. A biosensor comprising a first electrode, a sensing layer comprising a ZnO-based nanorod one end of which is attached to the first electrode, and a second electrode to which the other end of the ZnO-based nanorod is attached.
2. The biosensor of claim 1, wherein the ZnO-based nanorod is horizontally disposed on a non-conductive substrate and the first and second electrodes are formed on both ends of the nanorod.
3. The biosensor of claim 2, wherein the non-conductive substrate is selected from the group consisting of a Si02/Si, glass, quartz, pyrex, sapphire and plastic plate.
4. The biosensor of claim 1, wherein the nanorods are vertically aligned on a conductive substrate.
5. The biosensor of claim 4, wherein the conductive substrate is made of a material selected from the group consisting of a metal, silicone (Si), and a conductive oxide and polymer.
6. The biosensor of claim 1, wherein the ZnO-based nanorod is a ZnO nanorod, a ZnO nanorod doped with a heteromaterial, a core-shell ZnO nanorod having a shell coating of a heteromaterial, or a ZnO-nanorod coated with an organic material.
7. The biosensor of claim 6, wherein the heteromaterial used in the doped nanorod is selected from the group consisting of Mg, Cd, Ti, Li, Cu, Al, Ni, Y, Ag, Mn, V, Fe, La, Ta, Nb, Ga, In, S, Se, P, As, Co, Cr, B, N, Sb, H and a combination thereof.
8. The biosensor of claim 6, wherein the heteromaterial used in the shell coating is selected from the group consisting of GaN, A1N, InN, GaAs, InP, GaP and an alloy thereof.
9. The biosensor of claim 6, wherein the organic material is a polymer selected from the group consisting of polyethylene glycol (PEG), polyethylene imine (PEI) and a modifϊed-PEG.
10. The biosensor of claim 6, wherein the organic material is a polymer selected from the group consisting of polydiallyldimethylammonium chloride, polysodium 4-styrenesulfonate and diazo resin.
11. A process for preparing the biosensor according to any one of claims 1 to 10, comprising the steps of horizontally or vertically disposing the ZnO- based nanorod on a substrate, and forming an electrode at the tip portion of the nanorod.
12. The process of claim 11, which comprises growing a ZnO-based nanorod on a substrate, separating the nanorod from the substrate, dispersing the separated nanorod in an organic solvent, and placing the nanorod on a non-conductive substrate, and forming two ohmic electrodes on both ends of the nanorod.
13. The process of claim 11, which comprises epitaxially growing an array of ZnO-based nanorods on a conductive substrate, and then forming an electrode on the top layer of the array of ZnO-based nanorods.
14. A method for the detection of an antigen-antibody binding, a biomolecule, or interactions of biomolecules using the biosensor according to any one of claims 1 to 10.
15. The method of claim 14, wherein the antigen is streptavidin or a modified streptavidin; and the antibody is biotin or a modified-biotin.
16. The method of claim 14, wherein the biomolecule is selected from the group consisting of low-density lipoprotein (LDL), polynucleotide and polypeptide.
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