Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
  • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
  • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
  • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
  • B81C1/00087—Holes

Definitions

• the present invention relates to a method of fabricating a nanogap and a nanogap sensor, and, more particularly, to a method of simply fabricating a nanogap and a nanogap sensor at low cost using a semiconductor manufacturing process, with which the position and width of the nanogap can be easily adjusted.
• a nanogap can be applied to an electrode, so that the nanogap can be used to research the electrical characteristics of a nanoscale structure or can be utilized as a sensor for sensing an extremely small amount of chemical materials or biological materials.
• the nanogap is necessarily used to measure variation in electrical characteristics at the molecular level.
• Korean Patent Application No. 10-2004- 0082418 discloses a method of forming a nanogap electrode by placing a spacer on one side of a first electrode, forming a second electrode, and then removing the spacer.
• the method has disadvantages in that the processes therefor are complex, it is difficult to adjust the width of the nanogap, and it is impossible to form a plurality of nanogap electrodes simultaneously.
• the size of the formed nanogap depends on that of the nanostructure, and it is difficult to form the nanogap at a desired place.
• it has been difficult to economically and efficiently produce the nanogap in large quantities and thus it has been limited in use to the direct evaluation and analysis of the electrical characteristics of nanoscale materials such as single molecules, nanoparticles, protein and DNA.
• nanoscale materials have been able to be handled using electrodes having nanoscale gaps due to continuous advancement in semiconductor process technologies. If these technologies are used, it is possible to measure physical or electrical characteristics, such as conductivity etc. of a single molecule or nanoparticles .
• nanoscale electronic devices such as a nanoscale rectifier and a nanoscale transistor, have been developed by controlling the current flowing through a molecule.
• biotechnology such as a biological device used to observe the variation in electrical characteristics of protein, DNA and the like when they are placed between the electrodes having nanoscale gaps therebetween and medicine is administered to them, have rapidly advanced.
• an object of the present invention is to provide a method of conveniently fabricating a nano gap at a low cost using a semiconductor manufacturing process.
• Another object of the present invention is to provide a method of fabricating a nanogap sensor which can be used to research the physical and chemical characteristics of a nanoscale material using the nanogap which has been fabricated through the above method.
• a further object of the present invention is to provide a method of fabricating a nanogap sensor, which can be used to produce the nanogap sensor, having a predetermined size, in large quantities using the above nanogap and method of fabricating a nanogap sensor.
• Still another object of the present invention is to provide a method of observing the electrical and chemical characteristics of nanoscale material using the nanogap sensor fabricated through the above method.
• FIG. 1 is a schematic flow chart showing a process of fabricating a nanogap sensor according to an embodiment of the present invention
• FIG. 2 is a view for mathematically elucidating the determination of gap size (width) based on the thickness of silicon and the width of mask pattern to fabricate a nanogap sensor according to the method of the present invention
• FIG. 3 is a sectional view showing each step of the process of fabricating a nanogap sensor according to an embodiment of the present invention
• FIG. 4 is a view for elucidating the formation of silicon dioxide on a nanogap in an oxidation process
• FIG. 5 is a view showing the decrease in gap size after an oxidation process
• FIG. 6 is an electron microscope photograph of a nanogap obtained through a method of fabricating a nanogap according to the present invention
• FIG. 7 is an electron microscope photograph showing a gap size in the nanogap in FIG. 6
• FIG. 8 is an electron microscope photograph of a nanogap, in which the gap size before an oxidation process treatment can be compared with that after the oxidation process treatment, in the nanogap fabricated through a method of fabricating a nanogap according to the present invention
• FIG. 9 is a schematic view showing a state in which an antigen is detected by attaching an antibody to a nanogap sensor fabricated according to the present invention.
• FIG. 10 is a graph showing an experimental result using a nanogap sensor
• FIG. 11 is a schematic view showing a method of attaching a biomolecule to an existing nanogap sensor.
• FIG. 12 is a schematic view showing a state in which an antibody is directly attached to the surface of an electrode of a nanogap sensor fabricated according to an embodiment of the present invention, and an analysis antigen is bonded thereto.
• an aspect of the present invention provides a method of fabricating a nanogap, including anisotropically etching a substrate.
• the anisotropic etching of the substrate includes dry etching or wet etching the substrate to form a V-shaped section (V groove) thereon. More preferably, the anisotropic etching of the substrate includes wet etching using an etchant enabling the anisotropic etching.
• the present invention discloses a method of fabricating a nanogap by wet etching a silicon substrate using an etchant enabling the anisotropic etching as a preferred embodiment, but the present invention is not limited thereto.
• the substrate which can be used to fabricate a nanogap through the anisotropic etching, may be a silicon substrate, a silicon oxide substrate, a glass substrate, a ceramic substrate or a metal substrate.
• the metal substrate can be composed of gold, silver, chromium, titanium, platinum, copper, palladium, ITO (indium, tin oxide) , or aluminum.
• the nanogap can be fabricated using any the above substrates, which are commonly known in the related art, and with which the nanogap can be fabricated through dry or wet anisotropic etching.
• the method of fabricating a nanogap is performed using a semiconductor manufacturing process .
• a method of forming a pattern through chemical etching has been widely used in the related art to form a desired electronic circuit on a silicon substrate.
• the etching is classified as isotropic etching or anisotropic etching in accordance with the way of etching the silicon substrate.
• the isotropic etching or anisotropic etching can be adjusted depending on the kind of silicon substrate and the kind of etchant for the etching.
• a method of fabricating a nanogap through the anisotropic etching method is realized as the method of forming a nanogap.
• the term “nanogap” means "a gap” having a width ranging from several nanometers to several tens or hundreds of nanometers in the related art, but the size thereof is not limited to any specific range.
• a nanogap is generally used as a nanogap sensor for evaluating the characteristics of nanoscale molecule or analyzing cells, DNA, protein, or antigen-antibody complexes using a biological device by forming an electrode on the nanogap.
• the desired width of the nanogap can be easily and variously adjusted by adjusting the size of the mask pattern on the silicon substrate in accordance with the analysis object.
• the nanogap can be easily fabricated at a low cost by applying the anisotropic etching method used in the semiconductor manufacturing process. Further, it is possible to produce the nanogap in large quantities.
• anisotropic etching refers to an etching method in which the etched shape is directional because a specific face of the substrate is etched more rapidly than the other face of the substrate
• anisotropic etching used in the present invention refers to an etching method of causing a substrate to have a V-shaped section.
• isotropic etching refers to an etching method in which the substrate is etched such that both side walls of the formed nanogap are perpendicular to the plane of the substrate because the substrate is etched at the same speed in all directions. Accordingly, in the case of anisotropic etching, the width of the portion (gap) that is actually etched on the substrate is much narrower than in the case of isotropic etching, therefore a nanoscale gap can be easily formed.
• Silicon has two properties, that is, isotropic etching, having a uniform speed in all crystal directions, and anisotropic etching, having different speeds according to the crystal direction. All types of polycrystal silicon and amorphous silicon exhibit an isotropic property, but single crystal silicon can exhibit different properties, such as isotropy and anisotropy, according to the etching solution. Meanwhile, a ⁇ 100>, ⁇ 110>, or ⁇ 111> type silicon substrate is known as a silicon substrate which is commonly sold, well known and frequently used in the related art. Among these, an anisotropic etching able to forme a V- shaped section, which is required in the present invention, is the ⁇ 100> type silicon substrate.
• this silicon substrate which can be subjected to the isotropic etching, be used.
• any kind of silicon substrate may be used as long as the silicon substrate can be formed into a V-shaped section using anisotropic etching, and it is not limited to the ⁇ 100> type silicon substrate.
• etchants commonly known in the related art may be used as a material for performing anisotropic etching of the substrate using the wet etching according to the present invention.
• These etchants which are compounds for performing the anisotropic etching, can be manufactured by mixing KOH (potassium hydroxide) with water and isopropyl alcohol, and any one of TMAH (tetramethyl ammonium hydroxide) and EDP (ethylene diamine pyrocatechol) may be used as the etchant.
• KOH potassium hydroxide
• TMAH tetramethyl ammonium hydroxide
• EDP ethylene diamine pyrocatechol
• any etchant which can be used to perform anisotropic etching in the related art, such as semiconductor manufacturing technology, may be used to perform the anisotropic etching according to the present invention.
• a conventional semiconductor manufacturing process used in the present invention to form the nanogap on the silicon substrate may include the step of: depositing a mask material on the silicon substrate; applying a photoresist on the deposited mask material; developing the applied photoresist by performing ultraviolet exposure; exposing a portion of the substrate to be etched by removing the mask material, and removing the residual photoresist; and forming a nanogap by anisotropically etching the silicon substrate to have a V- shaped section (V groove) .
• the step of depositing a mask material on the silicon substrate may be a step of depositing a mask material on the silicon substrate based on the size (width) of a mask pattern calculated from the thickness of the silicon substrate and the size (width) of a desired nanogap. That is, when the size of the desired nanogap, that is, width (w 0 ) , is determined in the silicon substrate having a predetermined thickness (z), the width of the desired nanogap, that is, width (w 0 ) , is determined in the silicon substrate having a predetermined thickness (z), the width
• the etching angle ( ⁇ ) is previously set at a predetermined value according to the silicon substrate.
• the width of the nanogap on the silicon substrate fabricated according to the invention can be easily adjusted by adjusting the thickness (z) of the silicon substrate and the width (w 0 ) of the pattern of the mask material using the above equation.
• KOH, TMAH or EDP which are used to anisotropically etch the above silicon substrate, is preferably used as the mask material deposited on the silicon substrate. More preferably, silicon nitride (Si 3 N 4 ) may be used as the mask material. However, the mask material is not limited thereto, and any material such as SiO 2 , which is commonly known and used in the related art, may also be used as the mask material.
• the step of developing the photoresist applied on the mask material is preferably performed using an ultraviolet exposure.
• the step of removing the mask material is performed using an RIE (Reactive Ion Etching) method, by which a portion to be etched is exposed. Then, residual photoresist can be removed through a resist stripping process.
• the resist stripping process includes the steps of removing a photoresist by dipping it into acetone, cleaning the photoresist using methanol, and cleaning the photoresist using distilled water.
• the nanogap according to the present invention can be formed by anisotropically etching the silicon substrate using, preferably, an etchant enabling the anisotropic etching in order to have a V shaped section (V groove) .
• the method according to the invention may include the step of etching the silicon substrate using the etchant enabling the anisotropic etching, but is not necessarily limited thereto.
• the nanogap according to the present invention can be fabricated by etching the silicon substrate using methods commonly known in the related art, such as a dry etching method using 02 or CF4 gas in order to have a V shape. Accordingly, these various modifications, additions and substitutions are included in the scope and spirit of the present invention.
• the substrate used in the present invention is not limited thereto, but it is preferred that a ⁇ 100> type silicon substrate be used in the present invention.
• a method of fabricating a nanogap according to the invention preferably further includes a step of removing residual mask material from the silicon substrate.
• the step of removing residual mask material from the silicon substrate may be performed through, preferably, a wet etching method using HF, but is not limited thereto.
• the residual mask material may be removed through wet or dry etching using any commonly known method.
• the method of fabricating a nanogap according to the invention further include a process of removing buried silicon oxide (Si ⁇ 2 ) through a wet or dry etching method after the formation of the nanogap, together with the process of removing the residual mask material.
• both the residual material and the buried silicon oxide may be removed through the wet etching method using HF.
• the method of fabricating a nanogap according to the invention may further include a step of performing an oxidation process, which is a process of decreasing the size (width) of the nanogap, after the step of removing residual mask material from the silicon substrate.
• an oxidation process which is a process of decreasing the size (width) of the nanogap, after the step of removing residual mask material from the silicon substrate.
• the width of the nanogap fabricated through the above process can be decreased further through the oxidation process.
• the oxidation process is performed, as shown in FIG. 4, there occurs an effect in which silicon dioxide (SiO 2 ) is formed on the silicon substrate and thus the width of the nanogap is decreased.
• the oxidation process may be performed through dry oxidation in a furnace at high temperature, for example, about 1000 0 C, and may be performed through wet oxidation, in which the silicon dioxide is rapidly formed in large quantities and the size of the nanogap is thus decreased.
• the wet oxidation process requires less processing time than the dry oxidation process.
• the dry oxidation process exhibits higher density than the wet oxidation process.
• Silicon dioxide (SiO2) is formed by reacting silicon atom (Si) with oxygen (02) due to the injection of oxygen gas in the dry oxidation process.
• the present invention provides a method of fabricating a nanogap sensor using the. nanogap fabricated using the method of fabricating a nanogap according to the invention.
• the method of fabricating a nanogap sensor includes the steps of depositing an insulation material on the substrate on which the nanogap, fabricated using the above method, is formed, and forming a nanogap electrode.
• the nanogap according to the present invention is required to be used as a biological sensor for detecting the molecular characteristics of a biological sample or whether or not a biological samples is present by placing the biological sample, such as a nanoscale molecule, nanoscale cell or antigen-antibody, between the nanogaps .
• the nanogap sensor of the present invention can be realized by performing a process of forming an electrode, serving as a sensor, on the nanogap and additionally performing a passivation process .
• the electrode can be formed through a process of depositing a metal used as the electrode and a photo work.
• the photo work includes the steps of applying a photoresist, developing the photoresist according to a mask pattern using ultraviolet exposure, removing the metal forming the electrode, and removing the photoresist.
• the metal used to form the electrode is not limited as long as it has conductivity, and, preferably, is gold, silver, chromium, titanium, platinum, copper, aluminum, palladium, ITO or an alloy thereof. It is preferred that an electron beam deposition method, in which the electron beam has a long mean free path, be employed as the metal deposition process.
• a process of passivating portions other than the portion serving as a sensor in the nanogap sensor using a material such as AI 2 O 3 or SiO2 may further be performed.
• a smaller sample is sufficient at the time of measurement using the nanogap sensor because the material is not attached to portions other than the sensor portion in the nanogap sensor.
• the electron beam deposition method in which the electron beam has a long mean free path, may be used as the metal deposition process.
• Materials other than the above materials, which are insulation materials and with which the electron beam deposition can be performed, may be used as the passivation material.
• the present invention provides a nanogap sensor fabricated using the above methods.
• the nanogap sensor includes a voltage-current characteristic, and can detect the variation of current according to the concentration of the object for electrical, chemical, electrochemical or biological analysis, or detect the fact that a binding event occurring between the nanoscale object to b ⁇ analyzed and a specific bonded structure generates detectable variation in voltage- current characteristics.
• nanoscale analysis object refers to a cell, DNA, protein, an antigen-antibody or enzyme-substrate complex, or the like.
• the nanogap sensor according to the present invention is preferably used as a biological sensor.
• the nanogap sensor can be variously modified depending on the analysis object. For example, when DNA molecule is to be analyzed, the nanogap sensor may be used by securing DNA, both ends of which are provided with a thiol group, to an electrode and then fixing a gold particle etc., to which the DNA can be attached for analysis, thereon.
• the nanogap sensor when protein is analyzed, the nanogap sensor may be used by coating the electrode with glass, polymer, or ceramic, attaching a linker such as cysteine to the exposed portion of the electrode, and thus attaching the protein for analysis thereon. Further, when an antigen-antibody reaction is analyzed, the nanogap sensor may be used by bonding a specific antibody to the above linker and then bonding a specific antigen thereto. As such, in the nanogap sensor according to the present invention, the nanogap sensor may be modified by those skilled in the art in various ways depending on the analysis object, and such modifications are included in the scope of the present invention.
• the analysis object such as an antibody
• the analysis object can be directly attached to the surface of the electrode formed in the nanogap, either via a linker or without the linker (see FIG. 12) .
• a linker or without the linker see FIG. 12
• the analysis object may be measured by attaching it to the bottom between the electrodes.
• the molecules for measurement can more easily be fixed by directly attaching the analysis object to the electrode, and a smaller amount of sample to be analyzed is thus required, compared to a conventional nanogap sensor.
• the nanogap sensor according to the present invention configured so that the analysis object can be directly attached to the electrode of the nanogap, is more useful, compared to the conventional nanogap sensor.
• the present invention provides a method of analyzing the characteristics of a nanoscale material and the electrical and chemical properties thereof using the nanogap sensor according to the present invention fabricated through the above method.
• FIG. 1 is a schematic flow chart showing a process of fabricating a nanogap sensor according to an embodiment of the present invention
• FIG. 2 is a view mathematically elucidating the determination of gap size based on the thickness of silicon and the width of the mask pattern for fabrication of a nanogap sensor according to the method of the present invention
• FIG. 3 is a sectional view showing each step of the process of fabricating a nanogap sensor according to an embodiment of the present invention
• FIG. 4 is a view elucidating the formation of silicon dioxide on a nanogap in an oxidation process
• FIG. 5 is a view showing a state in which a gap size is decreased, after an oxidation process.
• a mask material 20 is deposited on a silicon substrate 10 based on the size of the mask pattern calculated by the thickness of the silicon substrate 10 and the size of a desired nanogap (SlO) (see (a) in FIG. 3) .
• the thickness of the silicon substrate is not particularly limited as long as the silicon substrate is strong enough to allow metal to be deposited thereon in the nanogap sensor. As described above, it is preferred that a ⁇ 100> type silicon substrate, which can be anisotropically etched, be used as the silicon substrate 10.
• a silicon nitride (Si 3 N 4 ) film or SiO 2 which is not etched by an etchant such as KOH, TMAH or EDP for an anisotropic etching, be used as the mask material 20 deposited on the silicon substrate 10.
• the mask material 20 is deposited on the silicon substrate 10 through the step 10 (SlO) , and then a photoresist 30 is applied on the deposited mask material 20
• a nanogap having a V-shaped section is formed by anisotropically etching the silicon substrate 10 using the etchant (S50) (see (e) in FIG. 3) .
• a time required in the etching can be calculated by dividing the thickness of the silicon substrate 10 by the etching rate.
• FIG. 5 is a view showing a state in which the size of the nanogap is decreased through the oxidation process.
• silicon dioxide SiCt ⁇
• an electrode serving as a sensor, is formed, and then a passivation process is performed.
• the electrode is formed by depositing the metal used as the electrode on both side walls of the nanogap through a photo work. It is preferred that the process of depositing the metal be performed using an electron beam deposition method, in which the mean free path is long. It is preferred that, after the metal is deposited, the passivation process also be performed by depositing a passivation material using an electron beam deposition method, in which the mean free path is long.
• the metal used to form the electrode is not limited as long as it has conductivity, and, preferably, is gold, platinum, copper, or an alloy thereof.
• Example 1 The formation of a nanogap A ⁇ 100> type silicon substrate having a thickness of 500 ⁇ m and a size of 4 inches was provided, and KOH, which is used as an etchant, was provided.
• ⁇ value is approximately 54.6 ° (theoretically 54.74° ). Therefore, the ⁇ value and the thickness of the silicon substrate were determined, and thus it was determined that the thickness of the photomask was 714 ⁇ m using the Equation in FIG. 2, and thus a long rectangular photomask having the above thickness was provided.
• Si 3 N 4 which is only slightly etched by KOH, used as the etchant, was deposited on the provided silicon substrate to a thickness of 200 ran using LPCVD (Low Pressure Chemical Vapor Deposition) .
• LPCVD Low Pressure Chemical Vapor Deposition
• a photoresist (AZ5214E, manufactured by Clariant Ltd. in the United States) was applied on the deposited Si 3 N 4 to a thickness of 2 ⁇ m, and then the applied photoresist was developed by performing ultraviolet exposure.
• the photoresist having the rectangular pattern was removed, and the Si 3 N 4 was removed through reactive ion etching, thereby the portion of the substrate to be etched was exposed using the KOH.
• the electron microscope photograph in FIG. 7, as described above, shows the shape of the nanogap formed by performing anisotropic etching using the KOH.
• Example 2 The fabrication of a nanogap sensor
• a ⁇ value was set at approximately 54.6 ° (theoretically 54.74 ° ).
• the thickness of a photomask was 1.4 IM using the Equation in FIG. 2, and a long rectangular photomask having the above thickness was provided.
• Si 3 N 4 which is only slightly etched by the KOH, used as the etchant, was deposited on the provided silicon substrate to a thickness of 200 nm using LPCVD (Low Pressure Chemical Vapor Deposition) .
• LPCVD Low Pressure Chemical Vapor Deposition
• a photoresist (AZ5214E, manufactured by Clariant Ltd. in the United States) was applied on the deposited Si3N 4 to a thickness of 2 ⁇ m, and then the applied photoresist was developed by performing ultraviolet exposure. Then, the photoresist having the rectangular pattern was removed, and the Si 3 N 4 was removed through reactive ion etching, thereby a portion of the substrate to be etched was exposed using the KOH.
• the residual photoresist was removed and cleaned, anisotropic etching was performed using the KOH of 20% at 80 ° C for 60 ⁇ 90 sec in order to obtain a uniform and high etching rate, and thus a nanogap was formed.
• the etching rate was approximately 1.4 ⁇ m/min.
• the residual SiaN 4 on the silicon substrate was removed and cleaned through wet etching using HF of 49%, and then dry oxidation was performed in a furnace at a temperature of 1000 ° C.
• FIG. 6 is an electron microscope photograph of the nanogap formed by performing the anisotropic etching using the KOH and then performing the wet etching using the HF.
• Cr/Au which are electrode formation materials, were deposited using an electron beam depositor, and electrodes were formed through photo work, and then the portion other than sensing portion was passivated by depositing AI 2 O 3 using an electron beam depositor, thereby fabricating a nanogap sensor.
• Example 3 The measurement of biological materials using the nanogap sensor
• a linker which can stably bond with an antibody, was attached to a gold electrode portion exposed from the nanogap sensor, and then an anti-PSA (Prostate Specific Antigen) antibody was bonded thereto.
• an anti-PSA Prostate Specific Antigen
• a protein-G linker N-ends of which are tagged with three cysteines, was used as the linker.
• protein-G was modified and then used to stably bond an antibody to a solid support.
• the protein-G linker disclosed in Korean Patent Application No.
• the antibody was stably secured by tagging N-end of the protein-G linker with 1-5 cysteines. Particularly, it was found that protein-G bonded with 1-3 cysteines more stably secured the antibody. In this case, the complete protein-G may be used. However, it was found that when only Bl and B2 regions, which are antibody bonding portions, were selected and the N-end thereof was tagged with 1-5 cysteines, the same effect was obtained. Accordingly, in the present invention, the linker, in which the N-end in Bl and B2 regions of the protein-G was tagged with 1-5 cysteines, was used.
• cysteines tagged to the N-end of the linker have an affinity for gold, they were easily adsorbed on the gold electrode of the nanogap sensor according to the present invention.
• anti-PSA antibody were secured on the nanogap sensor provided with this linker, and then PSA was applied thereto to a concentration of 10 ng/ml, 1 ng/ml or 100 pg/ml, thereby the current of the nanogap sensor was measured.
• FIG. 9 schematically shows the state in which the antibody and antigen are applied on the nanogap sensor fabricated according to the present invention.
• FIG. 10 is a graph showing the result of measuring current variation with respect to the PSA concentration using the nanogap sensor fabricated according to the present invention.
• the nanogap and nanogap sensor can be simply and easily produced in large quantities using a semiconductor manufacturing process without using expensive equipment. Accordingly, it is possible to form various electrodes, measure the electrical characteristics of various materials, and apply the electrodes to various sensors.

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