WO2005108966A1 - Bio-capteur - Google Patents

Bio-capteur Download PDF

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Publication number
WO2005108966A1
WO2005108966A1 PCT/JP2005/005165 JP2005005165W WO2005108966A1 WO 2005108966 A1 WO2005108966 A1 WO 2005108966A1 JP 2005005165 W JP2005005165 W JP 2005005165W WO 2005108966 A1 WO2005108966 A1 WO 2005108966A1
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WIPO (PCT)
Prior art keywords
substrate
substance
electrode
detected
gate electrode
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PCT/JP2005/005165
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English (en)
Japanese (ja)
Inventor
Koichi Mukasa
Hiroshi Kida
Atsushi Ishii
Seiji Takeda
Kazuhisa Sueoka
Yoshihiro Sakoda
Agus Subagyo
Hirotaka Hosoi
Makoto Sawamura
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Japan Science And Technology Agency
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Publication of WO2005108966A1 publication Critical patent/WO2005108966A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • 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

Definitions

  • the present invention relates to a biosensor, and more particularly to a biosensor having a structure of a field effect transistor (hereinafter abbreviated as “FET”) or a single electron transistor (hereinafter abbreviated as “SET”).
  • FET field effect transistor
  • SET single electron transistor
  • a biosensor is a measurement device that utilizes the excellent molecular discrimination ability of a living body or a biological molecule, and in a narrow sense means a sensor that uses a biological substance such as an enzyme, a microorganism, or an antibody as a molecular recognition substance.
  • a sensor that detects a substance to be detected by using the interaction between molecules that occurs when a broad molecular recognition substance recognizes the substance to be detected (molecular interaction detection sensor Means).
  • Patent Document 2 Alexander Star, Jean-Christophe P. Gabriel, Keith Bradley, and George Gruner, “Electronic Detection of Specific Protein Binding Using Nanotube FET Devices", Nano Letters, March 2003, Vol. 3, p.
  • An object of the present invention is to provide a biosensor having sensitivity far superior to that of the prior art.
  • a biosensor according to the present invention comprises a substrate, a source electrode and a drain electrode respectively formed on the surface of the substrate and connected to one another by ultrafine fibers, and a gate electrode disposed on the back surface of the substrate.
  • a specific substance that reacts with the substance to be detected is disposed on the back surface of the substrate or the gate electrode.
  • the channel between the source electrode and the drain electrode is formed of ultrafine fibers, an ultrasensitive biosensor can be obtained.
  • FIG. 1 A perspective view of a biosensor according to an embodiment of the present invention
  • FIG. 2 A schematic configuration diagram of the biosensor of Fig. 1
  • FIG. 3 A schematic view showing an embodiment of detecting a substance to be detected using the biosensor of the present invention
  • FIG. 4 A schematic view showing another embodiment of detecting a substance to be detected using the sensor of the present invention
  • FIG. 5 An enlarged schematic view between the insulating substrate and the gate electrode in the biosensor of FIG.
  • FIG. 6 A schematic configuration diagram showing an example of a method for growing carbon nanotubes in the biosensor of the present invention.
  • FIG. 8 A schematic perspective view showing the formation of a catalyst by the conventional method as a method of growth and formation of carbon nanotubes
  • FIG. 9 A schematic perspective view showing the formation of a catalyst according to an embodiment of the present invention as a method for forming a carbon nanotube growth '. 10) Schematic perspective view showing an example of arrangement of catalysts according to one embodiment of the present invention
  • FIG. 12 It is a view showing a state before dripping a solution, which is a biosensor without applying a method for preventing the influence of a solvent according to one embodiment of the present invention
  • FIG. 12A is a plan view, FIG. The cross section
  • FIG. 13 It is a view showing the state of the biosensor of FIG. 12 after dropping the solution, FIG. 13A is a plan view, and FIG. 13B is a sectional view.
  • FIG. 14 is a bio-sensor which has been subjected to a method for preventing the influence of a solvent according to an embodiment of the present invention, and is a view showing a state before dropping a solution
  • FIG. 14A is a plan view
  • FIG. 4B is a cross section
  • FIG. 15 A view showing the biosensor of FIG. 14 after dropping a solution
  • FIG. 15A is a plan view
  • FIG. 15B is a cross-sectional view.
  • FIG. 17 A diagram showing a modification of the structure shown in FIG. 16, FIG. 17A showing a state before pressing the gate electrode, and FIG. 17B showing a state after pressing the gate electrode 18)
  • FIG. 17A A diagram showing a modification of the structure shown in FIG. 16, FIG. 17A showing a state before pressing the gate electrode, and FIG. 17B showing a state after pressing the gate electrode 18)
  • Cross-sectional view showing an example of the structure for direct molecular modification of carbon nanotubes in the biosensor of the present invention
  • FIG. 22 A diagram showing an example of the gate electrode position in the structure shown in FIG. 21, and FIG. 22A is a view showing that the gate electrode is not in contact with the solution surface when the gate electrode is disposed on the sample solution.
  • FIG. 22B shows the case where the gate electrode is in contact with the solution surface when the gate electrode is placed on the sample solution.
  • FIG. 23 A diagram showing another example of the gate electrode position in the structure shown in FIG. 21, and FIG. 23A shows that when the gate electrode is not disposed on the sample solution, the gate electrode is a silicon portion
  • FIG. 23B shows the case where the gate electrode is not placed on the sample solution
  • FIG. 23B shows the case where the gate electrode is placed on the surface of the silicon oxide film on the carbon nanotube side when the gate electrode is not placed on the sample solution
  • Fig. 23C shows the case where the gate electrode is disposed on the surface on the silicon portion side of the silicon oxide film when the gate electrode is not disposed on the sample solution
  • Fig. 23D is the gate electrode on the sample solution. Shows the case where the gate electrode is placed on the side wall of the silicon part when not placed on the
  • FIG. 25 A diagram showing IV characteristic curve at the time of FITC detection by the biosensor of the present invention
  • FIG. 28 Figure showing another example of IV characteristic curve when detecting hemagglutinin using antigen-antibody reaction by the biosensor of the present invention.
  • FIG. 29 A figure showing still another example of IV characteristic curve at the time of detecting hemagglutinin using antigen-antibody reaction by the biosensor of the present invention.
  • FIG. 30 A figure showing still another example of IV characteristic curve when detecting hemagglutinin using antigen-antibody reaction by the biosensor of the present invention.
  • FIG. 32 A figure showing still another example of IV characteristic curve at the time of detecting hemagglutinin using antigen-antibody reaction by the biosensor of the present invention.
  • FIG. 33 A figure showing an example of IV characteristic curve at the time of detecting hemagglutinin using antigen-antibody reaction by sol-gel method by the biosensor of the present invention.
  • FIG. 34 A figure showing another example of IV characteristic curve when detecting hemagglutinin using antigen-antibody reaction in sol-gel method by the biosensor of the present invention.
  • FIG. 35 A figure showing still another example of IV characteristic curve at the time of detection of hemoglobin using antigen-antibody reaction by sol-gel method by the biosensor of the present invention.
  • FIG. 36 The antigen-antibody reaction in the sol-gel method using the biosensor of the present invention
  • FIG. 37 A figure showing still another example of IV characteristic curve when detecting hemoglobinetin using antigen-antibody reaction in sol-gel method by the biosensor of the present invention.
  • FIG. 38 A figure showing still another example of the IV characteristic curve at the time of detection of hemoglobin using antigen-antibody reaction by sol-gel method by the biosensor of the present invention.
  • FIG. 39 A diagram showing an example of an IV characteristic curve at the time of calmodulin detection using an antigen-antibody reaction by the biosensor of the present invention.
  • FIG. 40 A characteristic diagram showing the relationship between the dilution ratio of a calmodulin antibody and the current value at the time of calmodulin detection using an antigen-antibody reaction by the biosensor of the present invention.
  • FIG. 41 is a schematic view according to process showing an application example of the improved dispersion method of the present invention
  • FIG. 41A is a view showing a state in which pyrene is immobilized on an electrode
  • FIG. 42 is a step-by-step schematic showing another application example of the improved dispersion method of the present invention, FIG. 42A showing an electrode on a substrate and carbon nanotubes grown in a vapor phase, and FIG. 42B showing pyrene Figure showing carbon nanotubes immobilized and immobilized on pyrene after immobilization
  • FIG. 43 A schematic view showing still another application example of the improved scattering method of the present invention.
  • FIG. 44 A diagram showing an example of the electrical characteristics of carbon nanotubes crossing between the electrodes by the improved scattering method of the present invention.
  • FIG. 1 is a perspective view of a SET-type biosensor according to an embodiment of the present invention
  • FIG. 2 is a schematic configuration view of the SET-type biosensor of FIG.
  • the code “1” is a chip-like insulating substrate, and “2” is coated on the insulating substrate 1 and a surface such as a functional group such as a hydroxyl group, an amino group or a carboxylic acid group.
  • a thin film having a group in this embodiment, for example, a SiO thin film having a hydroxyl group
  • “3” and “4” are a source electrode and a drain electrode which are formed on the thin film 2 at predetermined intervals. At the opposite part of both electrodes 3 and 4, sharp points 5 and 6 are formed respectively (See Figure 1). In addition, between the tips 5 and 6 of both electrodes 3 and 4, a carbon nanotube (hereinafter abbreviated as “CNT”) 7 in which a defect is introduced is grown and formed. A gate electrode 8 is formed on the surface of the substrate 1 opposite to the thin film 2.
  • CNT carbon nanotube
  • insulating substrate 1 refers to a widely insulated substrate, specifically, a substrate made of an insulator, or one surface of a conductor or semiconductor such as metal. Alternatively, it means a substrate coated on both sides with an insulating film.
  • the thin film 2 does not have a functional group, that is, a thin film made of simple SiO or the like constituting the insulating substrate
  • an inorganic compound such as silicon oxide / silicon nitride, aluminum oxide or titanium oxide, or an organic compound such as an acrylic resin or polyimide is used for the insulating substrate 1.
  • an organic compound such as an acrylic resin or polyimide
  • metals such as gold, platinum and titanium are used for the electrodes 3, 4 and 8. The electrical connection between the electrodes 3, 4 and 8 is as shown in FIG.
  • CNTs are used as the nanotube-like structure, and by using this nanotube-like structure, a very fine channel can be formed, and hence high sensitivity is achieved. Can be obtained.
  • an air gap G is formed under the CNT 7.
  • a biosensor having a SET structure is configured.
  • the basic configuration of SET and FET is the same, in the channel serving as the current path, the two are different in that the channel of SET has a quantum dot structure and the channel of FET does not have a quantum dot structure. ing. If a minute portion of the quantum dot structure is formed in the channel, electrons accumulate in this portion and the amount of current decreases significantly, making it possible to sensitively detect a slight change in charge on the channel.
  • the current value between the source electrode 3 and the drain electrode 4 is sensitive to changes in the charge (more strictly, the spin electronic state) on the gate electrode 8 or CNT7. Change to In general, SET is more sensitive than FET. In addition, it is rare that SET characteristics are observed without modification after CNT formation.
  • the CNTs on the FET at the CNT formation temperature (high temperature of about 900 ° C.), the CNTs are partially formed. To form an island and show the current characteristics of SET. Also, it is large compared to the operating current (approximately The same result can be obtained by passing a current (about several mA).
  • the spin-electron state on the CNT changes indirectly or directly, so the source electrode 3 and the drain electrode generated at this time It is possible to detect attached molecules from the change in current between four.
  • the antibody antigen reaction can be used to detect a specific antigen or antibody).
  • microbes such as infectious virus and bacteria can be detected with high sensitivity and at high speed.
  • This method can be effectively used for prevention by early detection of infectious diseases and for research of microorganisms, and since the element (sensor) itself becomes extremely small, it is brought out to the field to detect infectious disease virus. And can be used for these studies.
  • FIG. 3 is a schematic view showing an aspect of detecting a substance to be detected using the biosensor of the present invention.
  • a source electrode 3 and a drain electrode 4 are formed on a thin film 2 formed on an insulating substrate 1.
  • the source electrode 3 and the drain electrode 4 are electrically connected by the CNT 7.
  • a protective film 12 of SiO force is formed on the CNT 7.
  • a specific substance (molecular recognition substance) 13 for example, an antibody which selectively reacts or adsorbs (interacts) with the substance to be detected (the substance to be detected) is formed.
  • the to-be-detected substance 14 for example, an antigen
  • the biosensor is roughly divided into a molecule detection portion 18 and a signal conversion portion 19. Therefore, in order to detect different substances 4 to be detected, the molecule detection portion 18 may be changed.
  • FIGS. 4 and 5 are schematic views showing another mode of detecting a substance to be detected using the biosensor of the present invention, and in particular, FIG. 5 shows the insulating substrate 1 and the gate in the biosensor.
  • FIG. 8 is an enlarged schematic view between electrodes 8;
  • the detection of the substance to be detected 14 is performed by interposing the sample solution 15 containing the substance to be detected 14 between the insulating substrate 1 and the gate electrode 8.
  • reference numeral “20” is a molecule that maintains the orientation of a specific substance (for example, an antibody), and “21” is a substance other than the substance to be detected present in the sample solution 15.
  • FIG. 5 shows how a substance to be detected (for example, an antigen) 14 is selectively reacted or adsorbed by a specific substance (for example, an antibody) 13.
  • FIG. 6 is a schematic configuration view showing an example of a method of patterning a catalyst and controlling the position and direction of CNT while applying an electric field.
  • “1” is an insulating substrate
  • “2” is a SiO 2 thin film constituting the insulating substrate 1 (which may be modified later)
  • “9a” and “9b” are examples of the insulating substrate 1 (which may be modified later)
  • a catalyst layer made of iron or the like patterned on SiO thin film 2, “7” is applied with an electric field
  • the CNTs are formed between the catalyst layers 9a and 9b, and the growth position, direction, number, chirality, characteristics, etc. are arbitrarily controlled. Further, “10” is a reaction vessel, and “11” is a hydrocarbon gas such as methane gas which is a raw material of CNT7.
  • the grown CNT 7 has a length of about several / im (for example, about 3 ⁇ m) and a diameter of about several nm, and is an ultrafine fibrous aggregate.
  • the shape of the four probe method is created using CNTs whose growth position, direction, characteristics, etc. are controlled as non-invasive electrodes.
  • the four-probe method four needle-like electrodes (for example, electrode A, electrode B, electrode C, electrode D) are placed on a straight line on a sample, and an outer two-probe (for example, electrode A constant current is applied between A and D, and the potential difference between the two inner probes (for example, electrode B and electrode C) is measured to determine the resistance value.
  • an outer two-probe for example, electrode A constant current is applied between A and D, and the potential difference between the two inner probes (for example, electrode B and electrode C) is measured to determine the resistance value.
  • the portion where the electrode and the channel (CNT) overlap is a high electric field electron beam or STM (Scanning Tunneling Microscopy) / AFM (Atomic Force) Microscope: An atomic force microscope is used to perform bending with a local applied electric field to integrate the electrode and the channel (CNT).
  • the defect introduction method of CNT for example, there is a method of annealing at substantially the same temperature (for example, about 800 ° C.) as that when producing CNT, and then naturally cooling it.
  • the defect of the CNT means that the shape of the CNT has changed, such as a part of carbon atoms jumped out by heat and barely connected in the state that the CNT is broken.
  • defect-introduced CNTs can be used to produce SETs operating at room temperature.
  • the case of using a defect-introduced CNT has been described, but it is also possible to use a defect-free CNT.
  • FIG. 7 is a view showing room temperature coulomb diamond characteristics by SET using CNT. This room temperature Coulomb diamond property can prove that SETs using the CNTs of the present invention are operable at room temperature.
  • the chip is coated with a SiO 2 protective film 12 in order to operate in solution.
  • the protective film 12 is provided, in some cases it is not necessary to provide the protective film 12 which is not limited to this.
  • the biosensor according to the present embodiment is placed in a sample solution 15 in which a substance to be detected 14 such as DNA is dissolved, and is operated with an alternating current using a resonant circuit, and the specific substance 13 and the substance to be detected By measuring the single electron interaction with 14, detection of the substance to be detected 14 (evaluation of surface charge distribution characteristics) can be performed.
  • a substance to be detected 14 such as DNA
  • a resonant circuit By measuring the single electron interaction with 14, detection of the substance to be detected 14 (evaluation of surface charge distribution characteristics) can be performed.
  • a semiconductor property of CNT is used to create a FET type or SET type transistor.
  • the fabrication method consists of the process of catalyst deposition by general lithography, CNT growth by thermal CVD, and electrode fabrication.
  • the force to form an electrode after CNT growth on a catalyst may cause phenomena such as peeling of the electrode from the substrate or cracking in the electrode, or the contact potential with the CNT may It may also affect the properties or strength, and it is necessary to consider the electrode material to obtain stable current characteristics.
  • Method 1 was used.
  • the solvent containing the molecule may cover the electrode, and the solvent covering the electrode surface affects the connection between the electrode and a measuring device such as a prober, so this is prevented
  • the method (the second method described later) was used.
  • a sample or a vapor containing a sample may affect the gate electrode. This could be avoided by protecting the CNT (the third method described later).
  • the current value changed because the substance to be detected was vaporized and attached not only to the gate electrode but also to the CNT surface. There was an example.
  • the first method is to deposit a catalyst on a Si ⁇ film using electron beam lithography to form a nucleus for the growth of CNTs.
  • Both surfaces of the m Si substrate were covered with a SiO film of about 300 nm.
  • the first method is this Si ⁇ membrane
  • transition metals such as iron, nickel, cobalt, molybdenum, tungsten, or their transition metal fine particles on 22 and using the active catalyst as the growth nucleus of CNT.
  • FIG. 8 is a diagram for explaining an example of a conventional method.
  • “1” is an insulating substrate of Si with a SiO film formed on both surfaces
  • “7” is CNT
  • “9a” and “9b” are catalysts
  • catalysts 9a and 9b are formed by evaporation one by one at a predetermined interval, and CNT 7 grown from one catalyst 9a reaches catalyst 9b which forms a pair. When it does, connection between catalyst 9a and 9b by CNT7 is made.
  • FIG. 9 is a diagram for describing an embodiment (first method) of the present invention.
  • a plurality of dot-like catalysts 9a-l, 9a-2, ..., 9a-n are formed side by side at the position 22a where one electrode is formed, and the other electrode is formed.
  • Positions 2 2b are also formed of multiple dot-like catalysts 9b-l, 9b-2, ⁇ , 9b-n force The above-mentioned multiple dot-like catalysts 9a_l, 9a_2, ⁇ , 9a- n are opposed It is formed to be.
  • FIG. 10 is a view showing an arrangement example of the catalyst 9 according to the present embodiment (first method).
  • the six catalyst arrays are arranged in close proximity so that the interval L1 between adjacent catalysts is 2 ⁇ m, and one catalyst array 9a_l, 9a_2, .., 9a_n and the other catalyst array 9b_l, 9b_2
  • the interval L2 between n and n is 9 n.
  • the number of installed catalysts 9, the interval Ll and the interval L2 can be set arbitrarily.
  • the more the number of electrode pairs on one substrate the more the re ,. This is because the number of conductive electrode pairs can be increased.
  • formation of a catalyst and an electrode is performed as follows.
  • the maximum number of electrode pairs that can be formed is 24 pairs.
  • the width of one electrode is about 500 ⁇ m at maximum, the number of catalysts that can be arranged in this area is at most three. In the future, further miniaturization of the catalyst, high bridge ratio with a large number, and conductivity Although there is a possibility that the yield will be improved, in consideration of the functions of the electrode and catalyst, limitations in manufacturing technology, etc., it is sufficient to form a plurality of catalyst pairs corresponding to one electrode pair. .
  • the introduction of a plurality of catalysts resulted in a yield of 20% to 60% of the conductivity yield. I was able to improve near.
  • the catalyst is deposited in one electrode within the stable control limit of photo lithography, and the number of catalysts can be increased up to three, up to 87.5%. The yield of the conductivity was recorded.
  • FIG. 11 is an enlarged perspective view of the catalyst 9.
  • the catalyst 9 comprises, for example, a support layer 25 made of Si or the like having a thickness of 50 nm, and an intermediate layer 26 made of transition metal such as Mo, Ta or W having a thickness of 10 nm formed thereon. It has a three-layer structure with a 3 nm-thick top layer 27 made of a transition metal such as Fe, Ni, or Co formed thereon. Therefore, the height H of the catalyst 9 is 63 nm and the straight light D is 2 ⁇ .
  • the catalyst 9 having such a multilayer structure is patterned by thin film formation techniques such as deposition, sputtering, ion plating, etc.
  • a hydrocarbon gas 11 such as methane or the like is injected to Grow CNT 7 on Catalyst 9.
  • the growth of CNTs 7 was performed according to the following procedure.
  • the insulating substrate 1 on which the catalyst 9 was formed was heated from room temperature to 900 ° C. for 15 minutes.
  • Ar was introduced into the reaction vessel 10 at a flow rate of 1000 sccm (gas flow rate for 1 minute).
  • methane and hydrogen were introduced at a flow rate of 1000 sccm and 500 sccm, respectively, for 10 minutes, and then the inside of the reaction vessel 10 was cooled to room temperature over 120 minutes.
  • Ar gas was flowed into the reaction vessel 10 at lOOosccm.
  • electrodes (the source electrode 3 and the drain electrode 4) were vapor-deposited on the insulating substrate 1.
  • the electrodes are formed by depositing Au or depositing Ti and then coating the surface with Au.
  • the latter is characterized in that peeling from the substrate and cracking in the electrode are less likely to occur.
  • the width of the electrode covering the catalyst is about 10 zm.
  • a method of dispersing CNTs on the electrodes (a ream, a so-called scattering method) is known.
  • the conventional balamaki method relies on chance and can not be controlled.
  • the inventor of the present invention has devised a new balamaki method (hereinafter referred to as “improved balamaki method”) which is essentially different from the conventional balamaki method.
  • improved variance method will be described in detail later.
  • a large number (about 50 to 400) of electrodes are formed simultaneously.
  • a solution containing a modifying molecule may be dropped onto the CNT, and depending on the amount of solution, the entire electrode may be covered.
  • a film is formed between the probe of the measuring device such as a prober and the electrode, and an accurate current value is obtained. There is a possibility that it can not be obtained.
  • FIG. 12 and FIG. 13 are diagrams for explaining a biosensor which does not undergo the second method, and in particular, FIG. 12 shows a state before dropping a solution, and FIG. It is a figure which shows the state after dripping.
  • 12A and 13A are plan views
  • FIGS. 12B and 13B are cross-sectional views. Since the size of the electrodes 3 and 4 is small in the conventional biosensor, as shown in FIG. 13, in many cases, the entire electrodes 3 and 4 are covered by the coating 28 formed by dropping the solution. Since the current value flowing between the electrodes 3 and 4 is as small as about 1 ⁇ A, if the film 28 exists between the probe of the measuring apparatus and the electrodes 3 and 4, it is not possible to accurately measure the current.
  • the length L3 (see FIG. 14A) of the electrodes 3 and 4 is about 1.5-3 times longer than in the case of FIG.
  • the coating 28 of the molecule that modifies the CNT 7 is formed by lengthening the length L 3 of the electrodes 3 and 4, a portion not covered with the coating 28 on the end of the electrodes 3 and 4 (FIG. See).
  • a probe of a measuring device such as a prober
  • the width W1 of the tip of the electrodes 3 and 4 is 10 ⁇ m
  • the width W2 of the portion to be probed is 150 ⁇ m
  • the length L3 is 500 zm.
  • the CNT 7 is in a state of being slightly curved between the electrodes 3 and 4 and an air gap G is provided between it and the outermost surface on the substrate 1 side. And the difference in thermal expansion coefficient with the substrate 1 is absorbed by its own deflection.
  • CNTs are said to have 2000 times the strength of iron of the same size, and, in fact, CNTs are hardly damaged even if they are directly molecularly modified and then washed.
  • CNTs readily interact with water and various other molecules to change the spin-electron state. This change appears as a change in current value. This actively enables use as a gas sensor, and also becomes a noise source when using a back gate electrode or a side gate electrode as a sensor.
  • the CNTs are prevented from interacting with the vapor such as solution, thereby reducing the noise.
  • An insulating adhesive can be used to form the insulating protective film, but it is also possible to use a passivation film widely used for spin coating.
  • the increase in current observed when water was applied to the back gate electrode was not observed due to the formation of the insulating protective film.
  • the formation of the insulating protective film makes it possible to ultrasonically clean the entire device and to wash the back gate electrode and the like with a stronger cleaning agent than ever before.
  • the gate electrode of the biosensor can be formed at various positions, and can have various structures depending on the application of the sensor and the ease of fabrication. Each structure of the biosensor gate electrode will be described below.
  • FIG. 16 is a cross-sectional view showing an example of the structure for molecularly modifying the back surface of the substrate.
  • the SiO film formed on the side opposite to the side on which the CNTs 7 are arranged in the insulating substrate 1 is molecularly modified with a specific substance (for example, an antibody) 13 to be detected (E.g.
  • the sample solution 15 containing the antigen is interposed between the insulating substrate 1 and the gate electrode 8.
  • Basic characteristics as a sensor are the same as other structures. That is, when molecules adhere to the SiO film formed on the substrate, the value of the current flowing between the source electrode and the drain electrode changes. Read For example, by applying fluorescent molecule FITC (fluorescein isothiocyanate) to the gate electrode 8, the current value is changed.
  • fluorescent molecule FITC fluorescein isothiocyanate
  • an SiO membrane is used as an example of antibody-antigen reaction.
  • the entire surface of the back of the surface on which insulating electrodes 1 and 3 and the electrodes 3 and 4 and the CNT 7 are disposed can be modified. Therefore, as compared with the case of modifying CNT7, it can be molecularly modified in a large area, so it is suitable for detection targeting many molecules. Further, on the back surface of the insulating substrate 1, the electrodes 3 and 4 and the CNTs 7 do not exist, so that the uniformity of the modified surface is not disturbed. In addition, since the CNTs 7 are not directly modified, it is possible to avoid the damage of the CNTs by washing after use. Furthermore, since a mirror surface silicon oxide film surface can be formed by polishing the modified surface, it is extremely effective for immobilizing molecules (such as histags) for immobilizing antibodies and the like.
  • the back surface of the insulating substrate 1 as a modified surface, it is possible to cover and protect the electrodes 3 and 4 and the CNTs 7 disposed on the opposite surface (surface) with a protective film such as an adhesive S it can.
  • a protective film such as an adhesive S
  • the back surface of the insulating substrate 1 is used as a modification surface, cleaning and reuse of the device can be easily performed after the reaction. For example, it can withstand dozens of washings with water or imidazole.
  • FIG. 17 is a diagram showing a variation (variation) of FIG.
  • a glass insulating film 40 covering the device is formed using a silanized coupling agent.
  • a specific substance (for example, an antibody) 13 is immobilized on the glass insulating film 40, and a sample solution containing a substance to be detected (for example, an antigen) is dropped and dried. Press
  • this structure is equivalent to a top gate at first glance, it is physically The structure is close to the back gate sensing mechanism.
  • the sample and the gate electrode are disposed on "glass" which is highly insulated compared to the silicon substrate, and it becomes easy to shut out the leak.
  • the distance between the CNT and the gate electrode may be long, and the FET-like nature of the CNT may be weakened.
  • FIG. 18 is a view showing an example of a structure for direct molecular modification of CNT.
  • the direct electron modification of CNT 7 makes the change of the spin-electron state on CNT 7 by the modified molecule larger than that of the non-nogate 8 electrode, so this structure has high sensitivity. There is.
  • FIG. 19 is a view showing an example of a structure for indirectly molecularly modifying CNT.
  • CNT7 is coat
  • the change of the spin electronic state caused by the modifying molecule or the molecule attached to the surface in the insulating thin film 30 causes a change of the spin electronic state of the CNT7, resulting in a change of current.
  • This structure has features of molecular modification of the back gate electrode 8 and direct molecular modification of the CNT7, and has high sensitivity and stability.
  • an island is created near the CNT on the substrate and used as a gate.
  • This structure does not require time-consuming labor such as molecular modification of the back surface of the substrate (back gate electrode), and also has features such as no damage to CNT7 itself caused by direct modification of CNT7. doing.
  • This is a suitable structure for SET.
  • the current characteristics are stabilized by covering the CNT and a part of the electrode with an insulating protective film.
  • FIG. 20 is a schematic configuration diagram for illustrating still another structure, and is a view showing an application example of the structure shown in FIG. 16 in which the back surface of the substrate is molecularly modified.
  • the electrodes 3 and 4 are disposed opposite to each other on the insulating substrate 1 with the CNTs 7 therebetween, and a back channel is formed on the opposite surface. That is, a concave portion 16 serving as a channel is formed on the back surface of the insulating substrate 1, and a liquid containing a detection target substance is attached to the concave portion 16 so that the target substance can be detected on the back surface of the insulating substrate 1. It is done.
  • insulating substrate 1 has an oxide film (SiSi) on the surface of silicon (Si).
  • a recess 16 to be a channel is formed in the silicon portion on the opposite surface.
  • the silicon portion is suitable for forming a reaction region (recess 16) because it is easy to physically or chemically etch and make a hole. Also, according to the method of forming an oxide film on silicon, it is possible to increase the sensitivity by thinning the silicon oxide film (SiO 2).
  • the recess 16 faces downward, but if it is a small amount of liquid such as several ml, the surface tension of the liquid does not cause the liquid to spill downward, so this back side
  • the channel surface may be directed either up or down. When the back channel surface is directed downward, the amount of evaporation of the sample solution can be suppressed, and stable IV characteristics can be obtained.
  • FIG. 21 is a view showing a modification (variation) of FIG. 20, in which the recess 16 is facing upward.
  • a chemical reaction of the sample occurs in the recess 16. Even if it is upside down, water droplets do not fall off due to the surface tension of water.
  • the surface of silicon thin film (Si) Normally covered with an oxide film (SiO 2), but if it is chemically scraped from the opposite side, the surface
  • the recon oxide film (SiO 2) can be exposed. Resists silicon oxide film compared to silicon
  • the silicon wall beside the recess 16 constitutes a container and enhances the strength of the entire element.
  • FIG. 22 shows the case where the gate electrode is disposed on the sample solution to function as the lid of the recess 16, and in particular, FIG. 22A shows the case where the gate electrode as the lid does not contact the solution surface.
  • FIG. 22B shows the case where the gate electrode as a lid is in contact with the solution surface.
  • the lid S can be used as the gate electrode 8.
  • the strength of the device can be increased by the lid (gate electrode 8).
  • the lid (gate electrode 8) is in contact with the solution surface, and by exerting pressure on the entire sample solution 15, the effect of suppressing the movement of molecules in the sample solution 15 is expected. can do.
  • high pressure can be applied to the sample solution 15 at room temperature to enhance the effect of molecular motion suppression. Therefore, in this case, there is no need for transpiration and freezing of sample solution 15.
  • FIG. 23 is a view showing variations of gate electrode positions when the gate electrode is not disposed on the sample solution.
  • the gate electrode 41 when the gate electrode 41 is disposed on any one of the silicon portions, in FIG. 23B, the gate electrode 41 is on the CNT 7 side of the silicon oxide film (SiO 2).
  • FIG. 23C shows that when the gate electrode 41 is a silicon oxide film (SiO.sub.2),
  • FIG. 23D shows the case where the gate electrode 41 is arranged on the side wall of the silicon part.
  • the gate electrode is not disposed on the sample solution, and therefore, the gate electrode can be used in cases where it is not contaminated with the sample solution.
  • the variation shown in FIGS. 23B and 23D can be used in the case where the entire device is thinned.
  • FIG. 24 is a schematic configuration diagram for illustrating still another structure.
  • this structure also uses the substrate 1 itself as a channel (back channel), the channel 1 of the substrate 1 A probe 17 consisting of is provided.
  • the structure in which the back channel and the probe 17 are integrated as described above can be used, for example, as a probe of a scanning probe microscope.
  • the antibody or antigen is immobilized on the back surface of the insulating substrate 1, and then the sample solution 15 containing the antigen or antibody is dropped. This causes an antigen-antibody reaction to occur.
  • the sample solution 15 on the insulating substrate 1 is evaporated.
  • thermoelectric conversion element Peltier element
  • This transpiration process makes it possible to avoid electric noise, conductivity 'perturbation', etc. of the solution when the CNT biosensor is applied to the sample solution.
  • it is also effective to cool the sample solution with a thermoelectric conversion element (Peltier element) or liquid nitrogen to reduce the influence of solvents such as water.
  • solvents such as water.
  • the noise can be significantly reduced.
  • the sensor can be operated at a constant temperature, and the controllability can be greatly improved for use in fields where the outside air temperature changes significantly or for precise measurement at a constant temperature. be able to.
  • a gold gate electrode is pressed against the dried or frozen rear surface, and the IV characteristics are evaluated. Since the antigen and the antibody are sandwiched between the insulating substrate 1 and the gate electrode 8, the IV characteristics can be stably detected.
  • the gold gate electrode is formed, for example, on an aluminum substrate. Although similar effects can be expected to some extent with other metal gate electrodes, gold gate electrodes exhibit conductivity that is an order of magnitude higher than, for example, brass gate electrodes when comparing gate leakage current. It is effective in detecting errors due to leaks and defective products.
  • the glass thin film By bonding to the lower part of the substrate, that is, by sandwiching the glass thin film between the gate electrode and the substrate, the insulation of the gate electrode can be enhanced and it can be used as a non-defective product.
  • adhesion of glass also changes the IV characteristics.
  • FIG. 25 shows the IV characteristics when the gate voltage is 120 V and the concentration of the fluorescent molecule FITC is 0.64 4.
  • the vertical axis of the figure shows the value of current flowing between the source electrode and the drain electrode (hereinafter abbreviated as “source-drain current” in the figure) ( ⁇ ), and the horizontal axis shows the voltage between the source electrode and the drain electrode.
  • the values (V) (hereinafter abbreviated as “source-drain voltage” in the figure) are shown.
  • the dotted line in the figure is the IV characteristic curve before the fluorescent molecule FITC is attached, and the solid line is the IV characteristic curve after the fluorescent molecule FITC is attached.
  • the CNT biosensor of the CNT biosensor is directly modified with pyrene, and ⁇ _ [5 _ (3 '-maleinimido pylamino) _1-carboxypentyl imino diacetic acid (_ _ [5 _ (3'-aleimidopropylamimo)-1-carboxypentyl] iminodiacetic After bonding the acid (abbreviated below as "NA") to the back gate electrode, a solution containing Ni ions was dropped, and the conduction characteristics were examined according to the IV characteristics of each case.
  • Fig. 26 shows the IV characteristics when no electric field is applied to the gate electrode.
  • the ordinate represents the current value (A) flowing between the source electrode and the drain electrode
  • the abscissa represents the voltage value (V) between the source electrode and the drain electrode.
  • “di” is the IV characteristic curve after cleaning the back gate electrode
  • “nta” is the IV characteristic curve after NTA bonding
  • “ni” is the IV after dropping a solution containing Ni ions. It is a characteristic curve.
  • the current increases by raising the voltage between the source electrode and the drain electrode, the source-drain voltage in all the systems (that is, the di nta ni system) In the vicinity of 0 V, the current hardly increases, and the semiconductor property is observed.
  • the IV characteristic curve (di) after washing shows a significant decrease in current.
  • Ni ions are generated into the system, the current increases. Since NTA reacts not only with Ni ions but also with other divalent positive ions, it is possible to detect other divalent positive ions.
  • the C terminal of HA was cleaved at various levels (220, 250, 290, 320) to try for expression.
  • a gene was introduced into 293T cells, and expression of HA protein in cells was confirmed using a monoclonal antibody E2Z3 and a polyclonal antibody.
  • Western blotting confirmed that HA protein was secreted in the supernatant. A large amount of HA is expressed, and the supernatant is purified on a Ni 2 + column
  • HA is deposited on the SiO film back gate electrode by His tag attached in advance to the HA.
  • the antibody was immobilized on NTA, and given an HA antibody by the same procedure as described above to obtain an IV characteristic curve. These IV characteristic curves are shown in Figure 27- Figure 32.
  • the gate voltage was -20V.
  • FIG. 27 shows an IV characteristic curve when a solution containing Ni ions is given after NTA binding
  • FIG. 28 shows an IV characteristic curve when an HA antibody with a dilution ratio of the stock solution of 10-1 Q is given
  • Fig, 29 showing a is a diagram showing an IV characteristic curve when the dilution ratio of the stock solution gave HA antibody in 10 8, 3 0, dilution of the stock solution gave HA antibody for 10 7 shows the IV characteristic curve when
  • FIG. 31 shows the IV characteristic curve when the dilution ratio of the stock solution gave HA antibody in 10 6
  • Figure 32 dilution of the original solution HA of 10_ 5
  • the dotted line in the figure is the former case, that is, the SiO film back gate electrode has HA.
  • the solid line indicates that if the HA is pre-attached to the HA, It is a case where it fixes to NTA on SiO film back gate electrode.
  • hemagglutinin (HA) using such an antigen-antibody reaction can be achieved by using a sol-gel method, that is, by detecting the antigen-antibody reaction in the environment of the sol'gel, similar results can be obtained.
  • a sol-gel method that is, by detecting the antigen-antibody reaction in the environment of the sol'gel, similar results can be obtained.
  • the These IV characteristics are shown in Figure 33- Figure 38.
  • a solution containing Ni ion was given after NTA binding.
  • the gate voltage was 120 V.
  • FIG. 33 is a diagram showing the IV characteristic curve when the dilution ratio without the HA antigen gave HA antibody for 10 7
  • FIG. 34 the dilution ratio without the HA antigen 10-6 shows the IV characteristic curve when given HA antibody in
  • FIG 35 is a view showing the IV characteristic curve when the dilution ratio without the HA antigen gave HA antibody in 10 5
  • FIG. 34 the dilution ratio without the HA antigen 10-6 shows the IV characteristic curve when given HA antibody in
  • FIG 35 is a view showing the IV characteristic curve when the dilution ratio without the HA antigen gave HA antibody in 10 5
  • Fig, 37 showing the IV characteristic curve when the dilution rate gave HA antibody of 10- 6 after attaching the HA antigen, when given HA antibody dilution rate 10-5 after carrying thereon an HA antigen
  • Fig, 38 showing the IV characteristic curve of a diagram showing the IV characteristic curve when the dilution ratio after applying the HA antigen gave HA antibody of 10_ 4.
  • “ni” in the figure is an IV characteristic curve when a solution containing Ni ion is given after NTA bonding
  • HA is a membrane attached with a film of HA by the pre-attached Histag.
  • pBAD / glll almodulin was constructed.
  • the vector was introduced into E. coli LMG 194 to obtain a force modulin expression clone. This clone was inoculated into 2 ml of LB / Ampicillin medium and cultured overnight.
  • Curve (a) in the figure is an IV characteristic curve when washed after NTA binding
  • curve (b) is an IV characteristic curve when CaM is bound to NTA with a pre-attached histag
  • curve (c) ) is, IV characteristic curve when the dilution ratio of the stock solution gave CaM antibody of 10- 8
  • curve (d) shows, IV characteristic curve when the dilution ratio of the stock solution gave 10 7 CaM antibody of the curve
  • e the IV characteristic curve when IV characteristic curve when the dilution ratio of the stock solution gave CaM antibody of 10- 6
  • curve (f) is the dilution of stock solution gave CaM antibody of 10_ 4
  • curve (g) is a IV characteristic curve when the dilution ratio of the stock solution gave CaM antibody of 10-2.
  • the results of detection of CaM antibody and HA antibody using ELISA are shown in Table 1 below.
  • the measurement procedure is as follows. Dilute the primary antibody at the following dilution and let stand for 1 hour, The antibody (anti-mouse HRPO standard antibody) was diluted 5000-fold and allowed to stand again for 1 hour, and then a substrate having an absorption wavelength of 450 nm was generated with TMB chromogen to measure absorbance.
  • Table 1 shows that the ELISA is difficult to detect at a dilution of 6.1 X 10- b .
  • sol-gel method shows the sensitivity of the order of ELISA, others are detected in all 10 8 about dilutions have been made.
  • CNTs are grown on the Si substrate, electrodes are formed at both ends, and the back surface opposite to the surface on which the CNTs of the Si substrate are grown is activated with acid (sulfuric acid),
  • acid sulfuric acid
  • the NTA is immobilized by reacting 3-mercaptopropyl pill triethoxysilane) at 180 ° C.
  • Ni ion immobilize the antigen (CaM, HA) into which histidine has been introduced, react with the diluted antibody, wash, apply negative bias to the back of the substrate, and obtain IV characteristics. It was measured.
  • FIG. 40 is a characteristic diagram showing a change in current value when 1.5 V is applied between the CNT electrodes after the CaM antibody thus immobilized is reacted with the diluted CaM antibody.
  • the current value increased as the antibody concentration increased. Also, it was found that the detection of the antibody is possible in the dilution range of about 1 o 1 Q to 10 8 of the antibody stock solution.
  • the CNT biosensor when the CNT biosensor is applied to a sample solution, noise may be observed, which may cause problems in data reliability. Therefore, noise can be significantly reduced by evaporating the solvent (moisture) with a blower, a heater, a thermoelectric conversion element (Peltier element) or the like after dropping the sample solution (test liquid) onto the sensor.
  • This noise countermeasure is applied to the example to which the above solution is applied.
  • the sample solution (test liquid) can be cooled by a thermoelectric conversion element (Peltier element) or liquid nitrogen to reduce the influence of a solvent such as water. In particular, by freezing and insulating water, noise can be significantly reduced.
  • the biosensor of the present invention uses electrical signals, the time required for detection is extremely short because of the absence of a large number of chemical reaction processes. In fact, although the current characteristics were examined by the IV curve, it is possible to obtain the IV curve within a few seconds by the parameter analyzer
  • temperature control is required in PCR and the like conventionally known, temperature control is required.
  • temperature control can be performed. It is unnecessary, the structure is simplified, and the size can be reduced.
  • the RT-PCR method, the ICAN method, the LAMP method, and the like that can be used in an environment where the temperature is constant have a drawback that the detection time is long.
  • the biosensor of the present invention is capable of performing multiple types of sensing simultaneously on one sample that is not a single type of detection, and of simultaneously detecting multiple types.
  • multiple samples can be detected in parallel using multiple biosensors.
  • biosensor of the present invention using a nanotube-like structure in the channel is strong and can be used repeatedly, but it is inexpensive so that it can detect dangerous viruses etc. You can use it, throw it away.
  • T biosensors are provided side by side, and DNA probes, protein probes, and
  • glycolipid probes individually and simultaneously measure different biopolymers (DNA, proteins, glycolipids).
  • the nanotube-like structure is not limited to this. It is possible.
  • balamaki method As described above, as a method of bridging CNTs between electrodes, conventionally, a method of scattering CNTs on electrodes (Le, a method of scattering) is known. However, the conventional balamaki method relies on chance and can not be controlled. The inventor of the present invention has devised a new balamaki method (improved balamaki method) which is essentially different from the conventional balamaki method.
  • the advantages obtained by the modified backscattering method are mainly the following two points. First of all, it is possible to realize a high yield on conduction. Second, as a result of eliminating the need to use a high temperature process (growth furnace at about 800 900 ° C.) accompanying vapor phase growth, a substrate such as glass which can not withstand high temperature can be used, and Commercial CNTs can be used to connect the electrodes without using expensive growth furnaces.
  • a high temperature process growth furnace at about 800 900 ° C.
  • Commercial CNTs can be used to connect the electrodes without using expensive growth furnaces.
  • the first modified dispersion method that is, a method of modifying a substrate or an electrode with pyrene will be described.
  • a relatively high yield (electrical conductivity between the electrodes) can be obtained even by using the above-described modified dispersion method alone, but applying the modified dispersion method on a substrate in which CNTs once grown in a vapor phase are present. Can significantly increase the yield and achieve 100% conductivity. Yes (but the yield to operate as a FET is not 100%).
  • the yield is low (about 0 to 20%), but in the experiment of the inventor of the present invention, the yield of up to 87.5% (24 electrodes on one substrate is obtained by devising the catalyst). Conductivity was detected between the 21 electrodes in the wafer).
  • aqueous solvent instead of the force using an organic solvent such as DMF.
  • Water is considered to have less effect on the target molecule than organic solvents.
  • the improved backscattering method can be used even on a substrate on which an electrode such as Au has already been deposited.
  • FIG. 42A shows a bird's-eye view of the electrodes 3 and 4 and the vapor-grown CNT 44 on the substrate. Immobilizing pyrene on this substrate by the first improved scattering method and then dispersing CNTs creates a connection as shown in FIG. 42B to obtain conductivity between the electrodes.
  • FIG. 42B "44” is vapor grown CNT, and "45” is CNT that is scattered and immobilized on pyrene.
  • the substrate is further placed in a CNT growth furnace to allow vapor phase growth.
  • the CNTs are added to the pyrene solution in advance, and the CNTs are covered with pyrene in advance.
  • the CNTs are covered with pyrene in advance.
  • the yield of non-defective products can be improved by dispersing pyrene-modified CNTs on a substrate on which vapor-phase grown CNTs are present.
  • further electrode deposition on the CNTs results in the same high conductivity as before.
  • CNT could be passed between the electrode substrates on a normal transparent glass (containing Na) that melts at about 400 ° C.
  • the growth conditions of the CNT on the glass substrate by the modified scattering method are the same as the conditions of the modified scattering method on the Au electrode.
  • a substrate such as glass
  • an optical microscope a fluorescence microscope, a laser microscope, etc.
  • the device can be operated while observing the state of the sample or substrate with a force microscope.
  • glass substrates are cheaper and easier to process than silicon substrates and the like, and are promising as substrates for future CNT elements having high insulating properties.
  • the conditions for deposition of thin film electrodes are expected to be different from those of glass.
  • CNT elements are formed on an insulating film formed on a silicon thin film, but sometimes a bulk current may be detected. That is, this is a phenomenon in which a defect occurs in the insulating film and the current leaks into the silicon substrate. If a glass substrate is used, there is no such a concern in the first place, but if the glass plate is bonded to a silicon substrate for which a leak has already been detected, the leak will stop and the FET state can be reproduced. Therefore, the non-defective rate can be increased.
  • the use of a glass substrate has merits that can not be considered from conventional semiconductor devices. In particular, since the heat absorption is reduced, the device can be easily cooled.
  • the transparency of glass facilitates processing. Specifically, if a positioning mark is deposited on one side of the glass, it is possible to position the element or the like S using the position on both sides.
  • the force using pyrene for CNT immobilization is not limited to this. It is also possible to perform the modified dispersion method using a substance other than pyrene. It is for example, other molecules having a benzene ring can be substituted. Specifically, for example, lysine can be used. Generally, the larger the number of benzene rings, the higher the van der Waals force acting with CNT and the easier it is to stabilize. It is necessary to strengthen the binding constant for immobilization.
  • a molecule with two or more arms consisting of benzene rings immobilizes only CNTs that match the angle formed by the two arms, so even if it has low purity CNTs, only those with an appropriate thickness can be selectively used. It can be immobilized on
  • the CNT 45b is too thick and can not be immobilized on the substrate.
  • the CNTs are arranged along the steps of the crystal surface (steps of atoms generated on the crystal surface) or by electrophoresis. It is also conceivable to arrange CNTs in solution. Furthermore, it is also conceivable that the current flowing in the benzene ring of CNT itself forms a magnetic field or FET is applied to CNT by applying a magnetic field to CNT or the like.
  • the main methods of producing a sensor that utilizes the electrical properties of CNTs can be classified into two broad categories.
  • One is a method in which dispersed CNTs are added between electrodes fabricated on a substrate to utilize CNTs spread between the electrodes, and the other is using a catalyst in the presence of high temperature gas
  • This is a method of growing CNTs and manufacturing electrodes later. Since the former uses CNTs produced by arc discharge, it is a problem to efficiently deliver CNTs between force electrodes that can use CNTs with few defects. The latter allows one CNT to be passed between the electrodes, and although the analysis is quiet, there is a high possibility that CNTs will have defects during CVD growth, and the yield is a problem.
  • the CNT sensor substrate is basically manufactured using the former method, but by chemically modifying the electrode preparation planned site on the silicon oxide substrate with the CNT affinity molecule. The purpose was to pass CNT efficiently between the electrodes.
  • the specific method is as follows. A photoresist was coated on a silicon oxide substrate, and the electrode preparation portion was exposed and developed. Then immerse the substrate in the aqueous solution containing the silanization reagent Then, the silanization reagent was immobilized on the developed area by heating and heating, the resist was dissolved by lift-off, and the substrate was further heated. A solution in which acid-treated CNTs are suspended in dimethylformamide is added dropwise and left at 25 ° C. for 1 hour, the resist is coated again and the electrode portion is exposed and developed. After development, titanium and gold are sequentially deposited to form an electrode. Made. Atomic force microscopy (AFM) was used to observe the immobilized CNTs and to evaluate the electrical properties of CNT across the electrodes using a parameter analyzer.
  • AMF Atomic force microscopy
  • FIG. 44 is a diagram showing the electrical characteristics of CNTs across the electrodes, and is a diagram in which Isd when IV is applied between source and drain is plotted against Vg.
  • HA shown as a specific example is spike protein and protein that coats the surface of influenza virus, and therefore it can be detected by the biosensor of the present invention, and it can detect infectious diseases such as influenza, SARS, BSE etc. And can be detected at high speed.
  • the biosensor of the present invention uses an electric signal whose detection unit is small, the detection circuit can be made into a chip, and can be used as a portable and inexpensive detector. As a result, testing in the field becomes possible and can be provided to all medical institutions. This will serve as a defensive measure against the early detection of infectious diseases, as well as a countermeasure against bioterrorism. Also in the field of basic science, detection of the binding strength of intermolecular interaction by one molecule level by the biosensor of the present invention, and classification of virus and protein by current characteristics become possible. For this reason, it is possible to conduct basic experiments in drug discovery through searching for or designing molecules similar to antibodies. In addition, detection of one molecule can be performed over time. In addition, it can be used as a basic circuit of a spectral tropic antigen-antibody reaction detector.
  • biosensor of the present invention can also be detected by the biosensor of the present invention.
  • the target can be applied not only to liquid but also to gas, and it is also possible to measure the concentration of specific substances such as harmful substances in the atmosphere and other gases. .

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Abstract

Un bio-capteur, capable de détecter une substance cible à faible concentration et ayant une sensibilité extrêmement élevée. Une électrode source (3) et une électrode déversoir (4) sont constituées sur la surface d'un substrat (1) et raccordées électriquement via un nanotube de carbone (CNT) (7). Une électrode de plaque (8) est installée à l'arrière du substrat (1). L'arrière du substrat (1) est modifié avec un matériau spécifique (13) réactif à la substance à détecter. Un échantillon de solution (15) contenant la substance est fourni dans l'espace existant entre l'arrière du substrat (1) et l'électrode de la barrière (8). Le substrat peut être détecté à partir d'une variation de la caractéristique de la tension du courant entre la source et les électrodes déversoir (3, 4) survenant lorsque la substance réagit avec le matériau spécifique (13).
PCT/JP2005/005165 2004-03-23 2005-03-22 Bio-capteur WO2005108966A1 (fr)

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JPWO2016021693A1 (ja) * 2014-08-08 2017-07-06 日本化薬株式会社 電界効果型トランジスタおよびそれを用いたセンサ
JP2016178114A (ja) * 2015-03-18 2016-10-06 富士フイルム株式会社 熱電変換素子

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