JP4466109B2 - Micro-insulation-coated metal conductor, method for manufacturing micro-insulation-coated metal conductor, and cell electric signal detection device - Google Patents

Description

  The present invention relates to a minute insulating coating metal conductor that can be used as an electrode or wiring, and a method for manufacturing the minute insulating coating metal conductor. The present invention also relates to a cellular electrical signal detection apparatus to which a minute insulating coated metal conductor is applied.

  Electronic components, for example, semiconductor elements such as transistors, are increasing in density and miniaturization year by year. Among them, the importance of the fine metal wires connecting them is increasing. On the other hand, fine metal wires are becoming important not only as such conducting wires but also as electrode probes for electrochemical measurements and the like in recent years.

  For example, when connecting an element for evaluation of a semiconductor element, a metal thin wire of 20 to 50 μm is connected to a pad electrode extending from the element. However, as integration and miniaturization progress, a short circuit between adjacent thin wires becomes a problem.

  Therefore, in order to prevent the short circuit, a thin metal wire covered with an insulator has been proposed as proposed in Japanese Patent Laid-Open No. 8-293517. However, for example, as the current semiconductor element is manufactured by a semiconductor process of 130 nm, the current semiconductor element is further miniaturized and integrated, so that the element itself becomes too small and is 20-50 μm. It is very difficult to extend a pad electrode capable of connecting a fine metal wire from an element. For this purpose, there is a demand for a fine metal wire having a shape that matches the current element by making the fine wire itself thin. At present, there is no fine metal wire with an insulation coating diameter of 1 μm or less.

  On the other hand, the thin metal wire coated with insulation is also used as a probe for electrochemical measurement. For example, since the sensitivity of an electrochemical electrode probe is generally improved as the tip is thinner, it is very effective to use a thin metal wire with insulation coating. In particular, as an application of electrochemical measurement, measurement of electrophysiological characteristics of a living body has been carried out in recent years for the application of drug tests or biosensors, and it is effective to use a fine metal wire for this measurement. An action potential is generated when a cell is active.

  This action potential is generated when the ion concentration inside and outside the cell membrane changes with changes in the ion permeability of the cells, and the cell membrane potential changes accordingly. Thus, by measuring the potential and current changes associated with changes in the ion concentration in the vicinity of the cells (that is, ion current) using the electrodes, it is possible to detect the activity of the cells in response to the stimulus. At present, these measurements are performed by measuring the potential and current of cell membranes and the like by an electrochemical technique typified by the patch clamp method.

  A patch clamp method for performing electrical measurements on living organisms, particularly cells, is described in E. Neher and B.W. The measurement method developed by Sakmann is reported in Nature, 260, 799 (1976). In this method, a glass electrode probe is brought into close contact with the cell membrane surface, and only the portion that is attached to the glass tube by suction is broken, and the potential and current of the attached cell membrane are directly and electrochemically passed through an electrolyte placed in the glass probe. It is a method of measuring. At this time, an important point is the maintenance of electrical insulation from the outside of the membrane near the front end of the glass electrode. The patch clamp maintains high insulation by suction.

  Therefore, it is a very effective method that can measure the current and voltage that flow only through the membrane, and can measure the response by changing the electrolyte. However, in order to destroy the cell membrane, the intracellular signal substance will be lost. There is a drawback. Therefore, it has been desired to perform measurement without destroying cells alive. O. P. Hamil et al., Pflugers Arch. As reported in 391, 85 (1981), a method for measuring whole cells without breaking the membrane (so-called patch clamp whole cell method) was developed.

  This method is a kind of patch clamp method, in which a probe is brought into contact with a cell and sucked for measurement without breaking the membrane. In this method, as described above, the insulation from the outside of the cell is maintained, but in order to reduce the electric resistance of the electrode, a probe thicker than the normal patch clamp method must be used. This cannot be used, and since there is one electrode (the voltage application and current are the same, the voltage detection electrode is the same, excluding the reference electrode), it is necessary to include a correction circuit externally. There is a fault that cannot be measured easily. In addition, since the current flowing through the entire cell is measured through the membrane connected to the electrode, the current distribution that indicates which part of the cell membrane flows the most cannot be measured.

  On the other hand, as a method for measuring living cells, there is a method in which one or two thin glass electrodes that do not destroy cells are stabbed into the cells. In this case, two electrodes, a micro glass electrode for measuring membrane potential and a micro glass electrode for current that is energized to fix the membrane potential, are inserted into the cell by a micromanipulator under a microscope, and the patch clamp method is used. Thus, it was difficult to maintain the insulation between the electrode and the cell, and it was applicable only to large cells such as giant squid neurons. This is because in a large cell, the signal current increases and the leakage current can be relatively reduced. When inserting into a normal cell, the probe electrode has to be thinned, and since the electric resistance increases and the current flowing through the electrode decreases, the signal current sufficiently large with respect to the leakage current cannot be detected. / N ratio was poor and could not be applied.

  As described above, the probe electrode is important for the electrical measurement of a living body, particularly a cell. The actual probe electrode uses a glass capillary filled with an electrolyte solution. The electrode is produced by applying heat to a normal glass tube to make the tip diameter 1 nm to 5 μm, as described in the new patch clamp experiment technique method (Yasunobu Okada, edited by Yoshioka Shoten 2001). Further, in order to easily maintain the insulation between the electrode tip and the cell membrane, an operation for processing the tip is performed by applying heat called heat polish. By this operation, the end face becomes wider and smoother. Further, an electrolyte solution serving as a conductor is injected into the electrode. In the method of filling this liquid, the tip of the glass electrode is immersed in a target solution, a syringe or a pump is attached to the opposite side, the electrolyte solution is sucked from the end, and the probe electrode is filled.

  When handling the completed probe electrode, it is necessary to continue to apply pressure from the outside so that the filled electrolyte does not leak. Naturally, since the conductor portion is an electrolyte, the electrode itself has a high electric resistance, the tip diameter is 1 nm to 5 μm, and the electric resistance is about 1 to 10 MΩ. Therefore, if the electrical resistance is to be lowered to increase the S / N ratio, the electrode must be thickened or the electrolyte concentration must be increased. If the electrodes are made thicker, some cells cannot be measured due to their size. On the contrary, if the electrode is made thinner, the restriction of the cell is eliminated, but not only the resistance becomes high, but it becomes difficult to contact the cell from the point of strength. In addition, it becomes difficult to fill the electrolyte up to the tip.

  On the other hand, when the electrolyte concentration is increased, the cell membrane is a semi-permeable membrane, so there is a significant difference in osmotic pressure from the bath solution (solution around the cell). It becomes difficult to determine whether an electric signal generated from the pressure difference is detected. Therefore, a probe having a thin tip that has low resistance and no restriction on cells has been desired.

Furthermore, due to the recent development of communication technology, there is concern about the danger that electromagnetic waves from communication devices will affect the living body. Therefore, electrophysiological measurement with an alternating current is desired for living bodies, particularly cells. However, the electric part of the electrode used in the current measurement method typified by the patch clamp method is an electrolyte solution in the glass tube, and the charge is the ions, so a particularly high frequency alternating voltage was applied. As in the case, there was a drawback that electrophysiological measurement of cells responding at high speed was not possible.
JP-A-8-293517 Nature, 260, 799 (1976) Pflugers Arch. 391, 85 (1981)

  In this way, when miniaturized elements and electrical components are connected, there is a possibility that the connected conductors may be short-circuited on elements that are currently integrated, and in order to prevent this, the elements are covered with an insulator, and the elements Therefore, it is necessary to have a thin conductor wire that can be connected to the cable.

  In addition, when one cell such as a nerve cell or an oocyte is measured alive as one of the electrochemical measurements, an electrode probe with the thinnest tip is inserted into the cell to minimize damage to the cell. It is necessary to measure in as short a time as possible. However, the probe electrode with a thin tip has a problem in terms of strength as well as an increase in electrical resistance and a poor S / N ratio. Furthermore, since an electrolyte is used, electrophysiological measurement for high frequencies has not been possible at present. Therefore, a probe electrode having a thin tip, strength that can be inserted into a cell membrane, and low electrical resistance is required.

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a method for manufacturing a finely insulated coated metal conductor that is coated with an insulator, has a small diameter at the tip, has a certain degree of strength, and has low electrical resistance, and a minutely insulated coated metal conductor. Is to provide.
Another object of the present invention is to provide a cellular electrical signal detection device using the above-mentioned fine insulating coated metal conductor as an electrode.

The above problem is solved by the following means. That is,
The method for producing a finely insulated coated metal conductor according to the present invention comprises:
A first step of heating a part of a wire in which a metal material is sealed in a hollow insulator until the insulator is softened;
A second step of stretching the heated portion of the wire and cutting the wire;
It is characterized by having.

  In the method for manufacturing a finely insulated coated metal conductor according to the present invention, it is preferable that the wire is melted in the metal material having a melting point lower than that of the hollow insulator and encapsulated in the hollow insulator.

  In the method for producing a finely insulated coated metal conductor according to the present invention, it is preferable that the wire is dispersed in a resin material having a melting point lower than that of the hollow insulator and sealed in the hollow insulator. is there.

In the method for producing a micro-insulation-coated metal conductor according to the present invention, a catalyst selected from carbon nanotubes , metals, metal oxides, proteins, and carbon pieces carrying these at the cutting site in the cut wire. When the insulator for sealing them, to have a third step of applying a solution that contains suitable.

In the method for manufacturing a finely insulated coated metal conductor according to the present invention, in the second step, it is preferable that the wire is cut by stretching so that the major axis of the end face of the cut portion of the wire becomes 100 nm to 3 μm.

  In the method for producing a finely insulated coated metal conductor according to the present invention, the metal material is at least one selected from low melting point solder, gallium, aluminum, tin, gold, silver, copper, platinum, and iron. Is preferred.

In the method for producing a minute insulating coated metal conductor according to the present invention, it is preferable that a volume resistance value of the hollow insulator is 10 ⁵ Ωcm or more.

  In the method for producing a finely insulated coated metal conductor according to the present invention, the material of the hollow insulator may be at least one selected from glass, quartz, ceramics, Teflon (R), polyimides, and polycarbonates. Is preferred.

The finely insulated coated metal conductor of the present invention is
A hollow insulator;
An encapsulating material encapsulated in the hollow insulator, wherein the encapsulating material is made of a metal material having a melting point lower than that of the hollow insulator, or the metal material is dispersed and has a melting point higher than that of the hollow insulator. An encapsulant composed of a low resin material;
Comprising
At least one end is characterized in that the metal material is exposed from the hollow insulator, and the major axis of the end face of the one end is 100 nm to 3 μm.

  In the fine insulating coated metal conductor according to the present invention, it is preferable that the one end where the metal material is exposed is tapered.

  In the fine insulating coating metal conductor of the present invention, the metal material is preferably at least one selected from low melting point solder, gallium, aluminum, tin, gold, silver, copper, platinum, and iron. .

In the fine insulating coated metal conductor according to the present invention, it is preferable that a volume resistance value of the hollow insulator is 10 ⁵ Ωcm or more.

  In the finely insulated metal conductor according to the present invention, the material of the hollow insulator is preferably at least one selected from glass, quartz, ceramics, Teflon (R), polyimides, and polycarbonates. is there.

In fine insulating coated metal conductor according to the present invention, wherein the said metal material exposed at one end, and a carbon nanotube, a metal, metal oxide, proteins, and a catalyst selected them from carrying carbon pieces, these it is preferable that a mixture composed include, an insulating sealing material for sealing is attached.

The cellular electrical signal detection device of the present invention comprises a cellular electrical signal detection electrode to be brought into contact with a cell, and an electrical signal detection unit that detects electrical signals from the cellular electrical signal detection electrode,
As the electrode for cell electrical signal detection, the micro-insulation-coated metal conductor obtained by the manufacturing method of the micro-insulation-coated metal conductor of the present invention or the micro-insulation-coated metal conductor of the present invention is used. It is a feature.

  In the cellular electrical signal detection device of the present invention, the cellular electrical signal detection electrode includes a plurality of the minute insulating coated metal conductors, and the metal materials in the plurality of minute insulating coated metal conductors are the same material. Is preferred.

According to the present invention, there is provided a method for manufacturing a finely insulated coated metal conductor that is coated with an insulator, has a small diameter at the tip, has a certain degree of strength, and has low electrical resistance, and a minutely insulated coated metal conductor. can do.
In addition, it is possible to provide a cellular electric signal detection device using the above-described minute insulating coated metal conductor as an electrode.

  Hereinafter, the present invention will be described in detail. In addition, the micro insulation coating metal conductor of this invention is demonstrated with the manufacturing method of the micro insulation coating metal conductor of this invention.

(Micro-insulation coated metal conductor: hereinafter abbreviated as micro-conductor)
The manufacturing method of the microconductor of this invention has the 1st step which heats a part of wire, and the 2nd step which extends the heating site | part in a wire and cut | disconnects the said wire. And, if necessary, it may have a third step of applying a solution containing a catalyst that causes a specific chemical reaction with carbon nanotubes and an insulator serving as a dispersion medium to a cutting site in the cut wire. it can. Hereinafter, each step will be described.

-First step-
In the first step, a wire composed of a hollow insulator and a metal material sealed in the hollow insulator is used. Then, an arbitrary part of the wire is heated. This heating is performed until the hollow insulator in the wire is softened.

  The heating is performed by, for example, a heat treatment using a heater or a heat treatment that irradiates electromagnetic waves.

The metal material which comprises a wire is for functioning as an electrical-conduction part as a microconductor. By applying a metal material as the electrically conductive portion, for example, about 1 Wcm to 1 × 10 ³ Wcm, a very low resistance can be realized. Specific examples of the metal material include at least one selected from low melting point solder, gallium, aluminum, tin, gold, silver, copper, platinum, and iron. Among these, low melting point solder and gallium are particularly preferable from the viewpoint of ease of processing and conductivity.

  Among metal materials, for example, when a metal material having a melting point lower than that of a hollow insulator such as low melting point solder, gallium, aluminum, and tin is used, the metal material is melted and sealed in the hollow insulator. On the other hand, when using a metal material that can ensure sufficiently low resistance even when dispersed in a resin material such as gold, silver, copper, platinum, or iron, the metal material is dispersed in a resin material having a melting point lower than that of a hollow insulator. And can be enclosed in a hollow insulator. Examples of the resin material for dispersing the metal material include epoxy resin, polymethyl methacrylate (PMMA), polystyrene, polyvinyl alcohol (PVA), polyethylene, polyethylene terephthalate (PET), polyether, and polyester.

The hollow insulator constituting the wire is intended to function as an insulating portion as a fine conductor. This insulating material does not need to be a complete insulating material, and may be as conductive as is generally regarded as a semiconductive material. However, in order to improve the S / N ratio, it is 10 ⁵ Ωcm or more. It is preferable to have a volume resistance value. The volume resistance value is more preferably 1 × 10 ⁵ Ωcm to 1 × 10 ¹⁵ Ωcm. Specific examples of the insulating material include glass, quartz, ceramics, Teflon (R), polyimides, and polycarbonates from the viewpoint of ease of processing. Among these, glass tubes are particularly preferable because they can be easily handled.

  The wire can be produced, for example, by melting and encapsulating a metal material in a hollow insulator, or by melting and encapsulating a resin material in which the metal material is dispersed in the hollow insulator. Specifically, a molten metal material (or a molten metal material-containing resin material) is poured into a hollow part of a hollow insulator and solidified in the hollow part. When flowing into the hollow portion, the hollow portion of the hollow insulator can be filled densely by sucking from one end of the hollow insulator.

-Second step-
In the second step, for example, the heated portion heated in the first step is stretched by pulling both ends of the wire (or fixing one end and pulling the other end). Since the heating in the first step is performed until the hollow insulator in the wire is softened, when a metal material having a melting point lower than that of the hollow insulator is used as the metal material, the metal material is melted in the hollow insulator Will exist. When the metal material is dispersed in a resin material having a melting point lower than that of the hollow insulator, the resin material is present in a melted state in the hollow insulator. For this reason, for example, by pulling both ends of the wire, the heated portion of the wire is stretched while the hollow insulator is softened and the metal material (or metal material-containing resin material) is melted, and then cut. The cutting may be performed by any known method, but the method of cutting and cutting as it is when stretching in a molten state may be simple.

  By cutting the heated portion of the wire in this state, the metal material is exposed only at the center of the cross section of the tip (cut portion) while being entirely covered with the hollow insulator, and a microconductor having a small tip is obtained. In addition, a fine conductor with a tapered tip can be obtained. If one end (tip) of the micro-conductor is tapered, it is easy to handle, and when used as a cell electrical signal detection electrode, it is easy to penetrate into the cell, and compared to the one with a constant thickness from the tip, It also has the feature of easily detecting current. In addition, since a metal is used, the strength is higher than that of a probe using an electrolyte. Therefore, it is possible to obtain a fine conductor that is covered with an insulator, has a small diameter at the tip, has a certain degree of strength, and has a low electric resistance.

  The major axis of the cut portion (tip) of the fine conductor is preferably 5 μm or less so that the fine electric device can be sufficiently wired. In addition, when used as a cell electrical signal detection electrode, it is preferably less than half of the cell to be measured so that it can be measured at a plurality of locations in the cell, but if it is 3 μm or less, it is eluted. The amount of ions that carry the current detected by the metal is sufficiently small, and noise can be reduced. Further, if the major axis is 100 nm or less, the resistance is increased, current detection is difficult, and the strength that can be inserted into the cell is problematic. Thus, the major axis of the cut portion (tip) of the fine conductor is preferably 100 nm to 3 μm, more preferably 100 nm to 1 μm, and still more preferably 100 nm to 500 nm.

  Here, the long diameter control of the cut portion (tip) of the fine conductor is performed by appropriately selecting the heating temperature, the tensile strength, and the pulling speed of the wire according to the hollow insulator type and the metal material type. . For example, when the heating temperature, the tensile strength, and the pulling speed are increased or increased, the major axis becomes smaller, and conversely, when the heating temperature, the tensile strength, and the tensile speed are lowered or slowed, the major axis tends to become thicker.

  In this way, for example, a fine conductor having a metal material exposed from a hollow insulator at least at one end and a major axis of a cut portion (tip) of 100 nm to 3 μm is obtained. Note that when a microconductor having the same configuration at both ends is manufactured, for example, the same operation as described above may be performed using the obtained microconductor as a wire.

-Third step-
In the third step, a metal material exposed at one end of the obtained microconductor is subjected to a catalyst that causes a specific chemical reaction with carbon nanotubes (hereinafter also referred to as a detection catalyst) and an insulating seal that seals them. A solution containing the stopping material or its precursor is applied. Thereby, the mixture of the said solution adheres to the exposed metal material, and comprises the electricity supply part of a microconductor.

  For this reason, the current-carrying part is composed of an insulator in which a plurality of carbon nanotubes and a catalyst that causes a specific chemical reaction are enclosed, and the plurality of carbon nanotubes are insulatively sealed with each other being electrically connected to each other. Enclosed in a stop material. Then, the detection catalyst is exposed on the surface of the insulating sealing material, and a part of the plurality of carbon nanotubes is exposed on the surface of the insulating sealing material through the insulating sealing material to constitute a current-carrying portion. Become. That is, a plurality of carbon nanotubes are exposed at a plurality of locations in a state where they are electrically insulated from each other. For this reason, the detection catalyst serves as an electrode part (chemical reaction part), the carbon nanotube serves as a conductor, and the insulating sealing material serves as an insulating film. In addition, the metal material (electrically conductive portion) exposed at the tip of the minute conductor is electrically connected to a part of the plurality of carbon nanotubes.

  In the current-carrying part, the first mode in which a part of the carbon nanotubes is electrically connected to the catalyst exposed on the surface of the insulating sealing material, and the detection catalyst and the carbon nanotubes are each independently in the surface of the insulating sealing material. The second mode exposed in the above and both modes are mixed.

  In the first aspect, the movement of electrons accompanying the chemical reaction by the detection catalyst is detected by the carbon nanotubes directly connected to the detection catalyst. On the other hand, in the second aspect, the movement of electrons accompanying the chemical reaction by the detection catalyst is detected by the carbon nanotubes exposed in the vicinity of the detection catalyst.

  For this reason, in any aspect, the carbon nanotubes detect in parallel the movement of electrons accompanying the chemical reaction by the detection catalyst at multiple locations in the current-carrying part, and the currents are electrically connected to each other in the insulating sealing material. Through the carbon nanotube thus formed, a current is extracted to the metal material (electric conduction portion) of the micro conductor.

  In addition, since the plurality of carbon nanotubes are sealed in the detection catalyst in a state where they are electrically connected to each other, the current detected in the current-carrying part has almost no loss, and the metal material (electric conduction part) ) Is extracted.

  In this way, the chemical reaction generated by the detection catalyst functioning as the electrode part is detected by the carbon nanotubes with extremely good conduction efficiency, so that the detection catalyst and a small amount of substance that causes a specific chemical reaction can be detected with high sensitivity. Can be detected. Furthermore, since it comprises a detection catalyst, carbon nanotubes, and an insulating sealing material, it can be handled stably in the atmosphere.

  Since the carbon nanotube detects the chemical reaction generated by the detection catalyst functioning as the electrode portion in parallel at a plurality of locations, the detection sensitivity can be improved.

  In general, substance detection by electrochemical methods is characterized by higher sensitivity as the electrode size becomes smaller, so the detection sensitivity can be increased by reducing the size of the catalyst that functions as the electrode part. Can do. Furthermore, when the microconductor is used as an electrode for electrochemical measurement, the potential window is widened. Specifically, for example, the potential window is about 4V to 8V.

  In addition, the form which gave the parallel electrical connection using the some carbon nanotube may be sufficient, and the form which comprised the electrode using one carbon nanotube may be sufficient. Since only a part of one carbon nanotube is exposed on the surface of the insulating sealing material, a substantial electrode portion (current-carrying portion) becomes minute, and highly sensitive electrical detection becomes possible.

  The carbon nanotube may be a single-walled carbon nanotube or a multi-walled carbon nanotube having two or more layers. Which carbon nanotube is used or whether both are mixed may be appropriately selected. Also, carbon nanohorns (horn-type ones whose diameter is continuously expanded from one end to the other end), carbon nanocoils (coil having a spiral shape as a whole), which are variants of single-walled carbon nanotubes Type), carbon nanobeads (with a tube in the center, which has a shape that penetrates spherical beads made of amorphous carbon, etc.), cup-stacked nanotubes, carbon nanotubes whose outer periphery is covered with carbon nanohorns or amorphous carbon Those that are not strictly tube-shaped, such as carbon nanotubes, can also be used.

  Furthermore, carbon nanotubes in which some substance is encapsulated in carbon nanotubes, such as metal-encapsulated nanotubes in which metals are encapsulated in carbon nanotubes, fullerenes or peapod nanotubes in which metal-encapsulated fullerenes are encapsulated in carbon nanotubes, are also carbon nanotubes. Can be used.

  As described above, in the present invention, in addition to general carbon nanotubes, any type of carbon nanotubes such as variants and various modified carbon nanotubes can be used without problems in view of their reactivity. can do. Therefore, “carbon nanotubes” in the present invention are all included in the concept.

  When carbon nanotubes are brought into contact with each other, when they are electrically connected to each other, the contact state changes due to bending of the electrode, etc., and mechanical strength and electrical strength may fluctuate, and sufficient performance may not be exhibited. In order to increase the electrical conductivity, the filling amount (encapsulation amount) of the carbon nanotubes must be increased. However, in this case, the amount of the insulator is decreased and the mechanical strength of the electrode itself may be decreased. .

  For this reason, it is preferable that the carbon nanotubes form a network structure in which the carbon nanotubes are electrically connected to each other by a chemical bond from the viewpoint of improving the electrical conductivity, mechanical strength, and electrode strength of the carbon nanotubes themselves. is there. Specifically, a crosslinked carbon nanotube structure in which a functional structure of a plurality of carbon nanotubes to which a functional group is bonded is chemically bonded to each other to form a network structure.

  The cross-linked carbon nanotube structure has a cross-linked site obtained by chemically bonding the functional groups of a plurality of carbon nanotubes. As the cross-linked site, the first structure in which a plurality of functional groups are cross-linked by a cross-linking agent is used. A second structure in which a plurality of functional groups are formed by chemical bonding is preferable.

  The first structure is a cross-linked structure in which residues remaining after the cross-linking reaction of the functional groups are connected by a linking group that is a residue remaining after the cross-linking reaction of the cross-linking agent.

  When the cross-linking agent has a property (self-polymerization) that causes cross-linking reaction between the cross-linking agents, the structure includes a polymer in which two or more cross-linking agents themselves are connected as a linking group. Since the density of substantial carbon nanotubes in the crosslinked carbon nanotube structure is reduced, the electrode may not have sufficient electrical conductivity and mechanical strength.

  On the other hand, if the cross-linking agent is non-self-polymerizable, the distance between the carbon nanotubes can be controlled to the size of the residue of the used cross-linking agent, so that the desired carbon nanotube network structure can be obtained with high reproducibility. Be able to. Furthermore, by reducing the size of the residue of the cross-linking agent, it is possible to configure the spacing between the carbon nanotubes in an extremely close electrical and physical state, and the carbon nanotubes in the structure can be closely packed. Can be structured.

  Therefore, if the cross-linking agent is non-self-polymerizable, the cross-linked carbon nanotube structure can exhibit the electrical characteristics or mechanical characteristics possessed by the carbon nanotubes in a very high dimension. In the present invention, “self-polymerization” refers to a property in which cross-linking agents can cause a polymerization reaction with each other in the presence of other components such as moisture or without the presence of other components. “Polymerizable” means having no such property.

  Here, if a non-self-polymerizable one is selected as the cross-linking agent, the cross-linked sites where the carbon nanotubes cross-link mainly have the same cross-linked structure. The linking group preferably has a hydrocarbon skeleton, and preferably has 2 to 10 carbon atoms. By reducing the number of carbon atoms, the length of the cross-linking site is shortened, and the gap between the carbon nanotubes can be made sufficiently close compared to the length of the carbon nanotube itself, and is substantially composed of only carbon nanotubes. A crosslinked carbon nanotube structure having a network structure can be obtained.

In the first structure, examples of the functional group include —OH, —COOH, —COOR (R is a substituted or unsubstituted hydrocarbon group), —COX (X is a rogen atom), —NH ₂ and NCO. It is preferable to select at least one group selected from the group consisting of these, and in this case, a crosslinking agent that can cause a crosslinking reaction with the selected functional group is selected.

  Preferred cross-linking agents include polyols, polyamines, polycarboxylic acids, polycarboxylic acid esters, polycarboxylic acid halides, polycarbodiimides, and polyisocyanates. At least one cross-linking agent selected from the group consisting of these can be used. Preferably, the functional group is selected from those capable of causing a crosslinking reaction with the selected crosslinking agent.

  It is possible to select at least one functional group and a crosslinking agent from the group exemplified as the preferred functional group and the group exemplified as the preferred crosslinking agent so as to be a combination capable of causing a crosslinking reaction with each other. preferable.

  In the first structure, as the functional group, —COOR (R is a substituted or unsubstituted hydrocarbon group) can be mentioned as a particularly preferable one. It is relatively easy to introduce a carboxyl group into a carbon nanotube, and since the resulting material (carbon nanotube carboxylic acid) is highly reactive, it is then esterified to convert the functional group to -COOR (R is substituted or It is relatively easy to obtain an unsubstituted hydrocarbon group. This functional group easily undergoes a crosslinking reaction and is suitable for forming a coating film.

  Moreover, a polyol can be mentioned as said crosslinking agent corresponding to the said functional group. The polyol is cured by a reaction with —COOR (R is a substituted or unsubstituted hydrocarbon group) and easily forms a strong cross-linked product. Among the polyols, glycerin and ethylene glycol are not only highly reactive with the above functional groups, but are themselves highly biodegradable and have a low environmental impact.

In the first structure, in the crosslinking site, the functional group is —COOR (R is a substituted or unsubstituted hydrocarbon group), and when ethylene glycol is used as a crosslinking agent, —COO (CH ₂ ) ₂ OCO— When glycerin is used as the cross-linking agent, if two OH groups contribute to crosslinking, -COOCH ₂ CHOHCH ₂ OCO- or -COOCH ₂ CH (OCO-) CH ₂ OH, and three OH groups contribute to crosslinking. if the _{-COOCH 2 CH (OCO-) CH 2} OCO-. The chemical structure of the cross-linked site may be any chemical structure selected from the group consisting of the above four.

  On the other hand, the second structure is a structure in which the functional groups of a plurality of carbon nanotubes are formed by chemical bonds, and the reaction that generates this chemical bond is one of dehydration condensation, substitution reaction, addition reaction, and oxidation reaction. It is preferable that

  In the crosslinked carbon nanotube structure having the second structure, the same functional group bonded to the carbon nanotube forms a cross-linked site by chemical bonding to form a network-like structure. The size of the cross-linking site for bonding between the carbon nanotubes is constant. Since carbon nanotubes have an extremely stable chemical structure, there is a low possibility that functional groups other than the functional group to be modified will be bonded. When these functional groups are chemically bonded together, the cross-linked site of the designed structure The crosslinked carbon nanotube structure can be made homogeneous.

  Since the second structure is a chemical bond between functional groups, the length of the cross-linked site between the carbon nanotubes can be shortened compared to the case where the functional groups are cross-linked using a cross-linking agent. The body becomes dense, and it becomes easier to achieve the effects specific to carbon nanotubes.

  In the second structure, the chemical bond between the functional groups is one selected from —COOCO—, —O—, —NHCO—, —COO— and NCH— in the condensation reaction, and —NH— in the substitution reaction. At least one selected from —S— and O— is preferably —NHCOO— for the addition reaction and —S—S— for the oxidation reaction.

In addition, as functional groups to be bonded to the carbon nanotubes before the reaction, —OH, —COOH, —COOR (R is a substituted or unsubstituted hydrocarbon group), —X, —COX (X is a rogen atom), — SH, —CHO, —OSO ₂ CH ₃ , —OSO ₂ (C ₆ H ₄ ) CH ₃ —NH ₂ and NCO can be mentioned, and it is preferable to select at least one group selected from the group consisting of these. .

  Among these, as the functional group, —COOH can be mentioned as a particularly suitable one. It is relatively easy to introduce a carboxyl group into a carbon nanotube. Moreover, the obtained substance (carbon nanotube carboxylic acid) is rich in reactivity, and easily undergoes a condensation reaction by using a dehydrating condensing agent such as N-ethyl-N ′-(3-dimethylaminopropyl) carbodiimide, Suitable for coating film formation.

  Thus, the crosslinked carbon nanotube structure having any of the crosslinked sites of the first structure and the second structure has a network structure with a plurality of carbon nanotubes via the plurality of crosslinked sites. Unlike the case where the carbon nanotubes are merely inadvertently contacted with each other, unlike the substantially isolated state, the excellent characteristics of the carbon nanotubes can be stably utilized.

  The detection catalyst is preferably made of fine particles or small pieces, for example. As described above, when the detection catalyst functioning as the electrode portion is made smaller, the detection sensitivity can be improved. Therefore, the size of the detection catalyst is preferably 1 nm to 100 μm, more preferably 1 nm in terms of average particle diameter. It is 10 micrometers, More preferably, it is 1 nm-1 micrometer.

Examples of the detection catalyst include metals, metal oxides, proteins, and carbon pieces carrying these. Examples of the metal include platinum, silver, gold, iron, copper, and silicon. As the metal oxide, for example, platinum black, acid iron, cobalt oxide, titanium oxide, tin oxide, indium oxide, gallium nitride, silicon oxide, acid zinc, ruthenium oxide, hafnium oxide, such as tungsten oxide and the like. Examples of proteins include enzymes. These can be used alone or in combination of two or more, but those that cause a chemical reaction with the substance are appropriately selected according to the substance to be detected.

As the insulating sealing material, any non-conductive material can be used without any problem, and an organic material or an inorganic material may be used. Here, the term “non-conductive” does not require a completely insulating material, and it may be a conductive level that is generally considered to be a semi-conductive material. The volume resistance value as the insulator is preferably in the range of 1 × 10 ⁵ Ωcm to 1 × 10 ¹⁰ Ωcm.

  The insulating sealing material is preferably a resin from the viewpoints of moldability, workability, precision, and the like. If a resin is used, a non-conductive substrate can be formed easily and with high accuracy by a conventionally known method such as injection molding or layer formation by coating and drying.

  Specific materials that can be used as the insulating sealing material include silicon oxide, silicon nitride, silicon oxynitride, titanium oxide, and niobium oxide from the viewpoint of not only non-conductive performance but also an outside air blocking function or a mechanical protection function. , Inorganic materials such as lithium niobate, strontium titanate, diamond, epoxy resin, polyimide, polyamide, polyamideimide, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, acrylic resin, polycarbonate resin, fluorine resin, amide resin, Examples thereof include various resins such as polyethylene terephthalate, polyurethane, polystyrene, polyacetal, silicone resin, Teflon (R) resin, polyether ketone, and polyketone, and other organic materials.

  Among these, polyether ketone, polyketone, polyimide, polycarbonate, polystyrene, and polyethylene are preferable, polyether ketone and polyketone are more preferable, and aliphatic polyether ketone is more preferable.

  The insulating sealing material may be chemically bonded to the carbon nanotube. When carbon nanotubes with extremely good conduction efficiency are encapsulated in a state of being chemically bonded to the insulator, the adhesion between the carbon nanotubes and the insulator is increased, and the carbon nanotubes are less likely to fluctuate within the insulator. For this reason, a very small amount of substance can be detected, and the potential window becomes wider when measuring a liquid.

  When the insulating sealing material is chemically bonded to the carbon nanotube in this way, for example, in the presence of a polymerization catalyst, polyhydric alcohol as a precursor (raw material) of the insulating sealing material, polymerization with the polyhydric alcohol is performed. A mixed liquid of carbon nanotubes having a functional group to react and a catalyst for measurement is used as a raw material, and this is applied to the tip of the fine conductor and then subjected to a polymerization reaction. In this polymerization reaction, polyhydric alcohols are polymerized with each other, polymerization of the polyhydric alcohol and the functional group of the carbon nanotube occurs, and a plurality of carbon nanotubes are chemically bonded to the polymer (insulating sealing material). They can be encapsulated in a polymer (insulating sealing material) while being electrically connected to each other.

  According to this production method, it is possible to synthesize a ketone group that improves the hardness of the polymer from a polyhydric alcohol, and in particular, a polyether ketone having a ketone group and an ether group and not containing an aromatic group, and carbon A current-carrying part composed of the nanotube and the detection catalyst is obtained.

  Here, examples of the functional group that undergoes a polymerization reaction with the polyhydric alcohol to be modified to the carbon nanotube include -COOR, -COX, and -NCO (R represents a substituted or unsubstituted hydrocarbon group, and X represents a rogen atom). Carbon nanotubes are relatively easy to modify-When COOH (carboxylic acid) is selected, polymerization occurs densely, and a more complex structure, that is, carbon nanotubes are closely attached to the polymer (insulator) and sealed, resulting in high effectiveness Can be obtained.

In addition, the bonding site where a plurality of carbon nanotubes and a polymer (insulator) molecule are bonded to each other is, for example, a functional group is —COOR (R is a substituted or unsubstituted hydrocarbon group), and glycerin is used as a polymer raw material. When used, if two OH groups contribute to the chemical bond with the carbon nanotube, it becomes -COOCH ₂ CHOHCH ₂ OCO- or -COOCH ₂ CH (OCO-) CH ₂ OH, and the three OH groups are cross-linked with the carbon nanotube chemistry. if contribute to the binding -COOCH ₂ CH (OCO-) a CH ₂ OCO-. The chemical structure of the crosslinking site may be any chemical structure selected from the group consisting of the above two.

  An aliphatic polyketone can be obtained from a polyhydric alcohol by a polymerization reaction involving an oxidation reaction, and an aliphatic polyether ketone can be obtained by further causing a polymerization reaction involving a dehydration reaction. That is, as the polymerization catalyst, an oxidation catalyst is used when producing a polyketone from a polyhydric alcohol, and a dehydration oxidation catalyst is used when producing a polyether ketone.

  However, when a polyether polyol is used as the polyhydric alcohol when producing the polyether ketone, an oxidation catalyst or a dehydration oxidation catalyst may be used. Here, the oxidation catalyst refers to a catalyst that oxidizes secondary hydroxyl groups and dehydrates and condenses the hydroxyl groups. Further, the polymerization catalyst may be liquid or solid, but the aqueous solution improves mixing with the polyhydric alcohol and can preferably cause a catalytic action. The polymerization catalyst is more preferably volatilized at a temperature lower than the thermal decomposition temperature of the polymer, or in the case of a non-volatile polymerization catalyst, the polymerization catalyst is partially or completely removed from the polymer.

Specifically, these polymerization catalysts are preferably at least one selected from sulfuric acid, nitric acid, hydrogen peroxide solution, Na ₂ Cr ₂ O ₇ , CrO ₃ Cl, and NaOCl, and particularly sulfuric acid is used. This is preferable because it easily causes a dehydration reaction and an oxidation reaction, is inexpensive, and has excellent handleability.

  The use amount (addition amount) of this polymerization catalyst is preferably 0.1 mg to 100 mg, more preferably 0.5 mg to 80 mg, and even more preferably 5 mg to 50 mg with respect to 1 g of the raw material. If the amount of the polymerization catalyst is too small, the polymerization reaction hardly occurs. Conversely, if the amount is too large, the resulting polymer (insulator) may foam.

  The polyhydric alcohol is preferably a polyhydric alcohol having a secondary alcohol and a primary alcohol in one molecule. Examples of such polyhydric alcohol include glycerin, 1,3,5-Trihydroxypentane, 1 , 2,4-Trihydroxybutane, 1,2,6-Trihydroxyhexane. In particular, glycerin is preferable because it is inexpensive and has a small environmental burden, and can easily cause a polymerization reaction using a dehydration and oxidation reaction catalyst.

  Further, if the carbon nanotubes are simply in contact with each other in the insulating sealing material, the contact state changes due to an external stimulus or the like, and the mechanical strength and electrical characteristics may fluctuate, so that sufficient performance may not be exhibited. Further, in order to increase the electrical conductivity, it is necessary to increase the filling amount of the carbon nanotubes. However, in this case, the amount of the insulating sealing material that is a binder is reduced, and the mechanical strength as the energizing portion is lowered.

  For this reason, it is preferable to use the above-mentioned crosslinked carbon nanotube structure. However, the crosslinked carbon nanotube structure may be formed by a crosslinking reaction together with a polymerization reaction with a polyhydric alcohol, or a previously formed crosslinked carbon nanotube structure and a polyhydric alcohol may be polymerized. In addition, when using the crosslinked carbon nanotube structure formed beforehand as a raw material, the functional group which carries out a polymerization reaction with a polyhydric alcohol needs to be modified.

  Through these steps, a fine conductor is obtained. The obtained microconductor is coated with an insulator as described above, and has a small diameter at the tip and at the same time has a certain degree of strength and low electrical resistance.

(Cell electrical signal detector)
The cellular electrical signal detection device of the present invention will be described with reference to the drawings. FIG. 1 is a schematic view showing an example of a cellular electrical signal detection device of the present invention. FIG. 2 is a block diagram showing an example of the internal configuration of the cellular electrical signal detection device of the present invention.

  A cellular electrical signal detection apparatus 10 shown in FIGS. 1 and 2 is an example installed in an optical microscope (not shown) for observing cells and electrodes, and two electrode probes 12 (electrical for voltage application and current detection) A signal detection electrode) and an operation unit 14 for operating the signal detection electrode are placed on a sample stage 16 of an optical microscope.

  As the two electrode probes 12, the above-described microconductor of the present invention (or one obtained by the manufacturing method thereof) is used. When a plurality of electrode probes 12 are used as described above, it is preferable to use the above-described microconductor of the present invention (or one obtained by the manufacturing method thereof) as the electrode probe 12 for current detection. Moreover, it is preferable that the metal material in each microconductor is the same material. As a result, measurement with low noise becomes possible. Furthermore, it is preferable to use a material that is as uniform in size as possible. If the size is the same with the same metal material, the noise can be effectively reduced and measured from the viewpoint of elution of the metal into the electrolyte.

  As the operation unit 14, for example, a high performance manipulator (manufactured by Unisoku Co., Ltd.) is used.

  Each of the two electrode probes 12 is fixed to the operation unit 14 so that the electrode probe 12 can be operated precisely. One of the electrode probes has a lead wire connected to a current amplifier 24 that amplifies an electric signal, and is then wired so that a signal is input to an electric signal detector 20 (for example, a multimeter). Yes. The other lead wire is connected to the power supply unit 18 so that an electrical stimulus, for example, a voltage can be applied. As described above, the two electrode probes 12 are brought into contact with the sample (cell), and electrical stimulation is applied from one side, thereby enabling electrophysiological measurement of the sample (cell). The power supply unit 18 and the electrical signal detection unit 20 can be collectively controlled by a computer, for example.

  Further, a pattern electrode 22 is installed on the optical microscope sample stage 16. The pattern electrodes 22 are connected to current amplifiers 24 that amplify electrical signals by the number of electrodes, and are wired so that signals are input to the electrical signal detector 20 (for example, a multimeter).

  By dropping a solution containing cells to be measured on the pattern electrode 22, the current distribution of one cell can be measured simultaneously.

  The pattern electrode 22 may be produced with an electrode width and an electrode interval equal to or smaller than the cell size. For example, if a cell of about 10 μm is fixed and measured on a comb-shaped pattern electrode 22 produced with an electrode width of 1 μm and an electrode interval, the current and voltage of the cell can be measured from five electrodes. That is, the electrode probe 12 is used for voltage application and current detection, and the cell current distribution can be measured from the pattern electrode 22. The pattern electrode 22 is preferably produced on a glass or quartz substrate. Thereby, the cells on the pattern electrode 22 can be observed even on the optical microscope sample stage 16. The pattern electrode 22 can be manufactured by a normal semiconductor manufacturing process including resist formation, exposure, development, metal vapor deposition, and lift-off, for example. The metal deposited on the pattern electrode 22 is a half mirror, which allows light to pass through and facilitates cell observation.

  When the above-described microconductor of the present invention (or the one obtained by the manufacturing method thereof) is applied as the electrode probe 12 (particularly, the electrode probe 12 for detection) of the cellular electric signal detection device 10 having such a configuration, Compared to conventional electrode probes (micro-conductors) using electrolytes, the following points are superior.

  1) Since metals and carbon nanotubes have lower resistance than conventionally used electrolytes, a weak current can be detected with a high S / N ratio. Specifically, the resistance of the electrode probe can be 10Ω to 10 kΩ. 2) The tip can be made very thin while maintaining a constant strength, and the potential and current of one cell can be measured easily and the current distribution of one cell can be measured. Moreover, it becomes high sensitivity because the tip is thin. Furthermore, a plurality of electrodes can be directly used for cells easily, and accurate measurement can be performed without a correction circuit. 3) Since the charge carrier is not an ion but an electron or a hole, a high-speed response of the cell can be detected. 4) For the same reason (carriers are electrons or holes), the attenuation with respect to the high frequency is smaller than that of the electrolyte, so that the cell responsiveness at the high frequency can be measured. 5) Furthermore, if the current-carrying part is composed of a carbon nanotube and a catalyst that reacts with a specific substance, the detection sensitivity for the specific substance can be increased.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, these examples do not limit the present invention.

<Example 1>
A fine insulator-coated metal conductor was prepared as follows. First, a glass capillary having a length of 10 cm, an outer diameter of 1.2 mm, and a capacity of 5 μl was filled while sucking low melting point solder heated to 70 ° C. and melted. A lead wire having a thickness of about 0.5 mm was inserted into the mouth opposite to the mouth from which the glass capillary solder was sucked. Next, the center portion of the filled glass capillary was heated at about 550 ° C. using Shimadzu Corporation micropipette tension MPT-1. Then, the other end of the glass capillary was fixed while the other end was pulled (conditions: tension 3 to 5 N), and the heated portion was stretched and cut. As a result, a fine insulator-coated metal conductor having a sharp tip and a major axis of 300 nm and a length of about 5 cm was produced. The electric resistance of the electric conduction part comprised with the metal material of the obtained conductor was 10 Wcm-100 Wcm. An electron micrograph of the tip of this conductor is shown in FIG. FIG. 3 shows that the conductor has a very sharp tip. 3A is a perspective view of the tip of the conductor, and FIG. 3B is a side view.

<Example 2>
Using the two microconductors produced in Example 1 as electrode probes for measurement, the electrical response of Paramecium, a single cell organism, was measured. As the configuration of the cellular electrical signal detection device used, one having the same configuration as that of the cellular electrical signal detection device 10 shown in FIGS. 1 and 2 was used (however, no pattern electrode was used). Specifically, two high performance manipulators (manufactured by Unisoku Co., Ltd.) are fixed to a sample stage 16 of an optical microscope (Olympus IX-70), and the electrode probes 12 are respectively attached to the manipulator (operation unit 14) at 45 degrees. Fixed at an angle. The lead wire extending from the electrode probe 12 is connected to the current amplifier 24, and the lead wire of the other electrode is connected to the power supply unit 18, so that the current to which the cell responds can be measured while applying a voltage to the cell. .

  First, a slide glass is placed on the observation part of the sample stage 16 of the optical microscope, and 50 μl of a culture solution containing Paramecium is dropped on the slide glass. Next, 10 μl of 10 mM nickel chloride, which is an anesthetic that stops movement of Paramecium cilia, is dropped. While observing with an optical microscope, 122 electrode probes are operated on a Paramecium that has stopped moving using a high performance manipulator, the electrode probe 12 for current detection is inserted into the Paramecium, and the electrode probe for applying voltage is used as a Paramecium. Contacted the surface. The photograph of the optical microscope observation at that time is shown in FIG. From FIG. 4, it can be seen that the fine conductor produced in Example 1 has a small diameter at the tip and sufficient strength so that it can be inserted into the Paramecium.

  Furthermore, FIG. 5 shows a graph in which the current that flows in response to the voltage applied from the electrode probe 12 in steps of 100 mV is plotted. As can be seen from FIG. 5, a weak current of 10 pA from one living cell can be measured.

<Example 3>
The electrical response of Paramecium, a single cell organism, was measured in the same manner as in Example 2 except that the pattern electrode was used. A method for manufacturing the pattern electrode is described below. The installation and operation of the electrode probe are as described in Example 3.

  The pattern electrode 22 was produced as follows. The pattern electrode 22 uses a quartz wafer substrate of Step Science as the substrate, and a resist agent (NPR9710 made by Nagase Sangyo) is used on this quartz substrate with a spin coater (manufactured by 1H-DX2 Mikasa) at 5200 rpm for 20 seconds. The film was applied, and heated to 100 ° C. for 2 minutes to form a film. Next, the resist-formed wafer was exposed for 3 seconds by using a mask having an electrode pattern having 4 electrodes (so-called 4 fingers) at an electrode interval of 2 μm using a mask aligner (manufactured by MA-20 Mikasa). Next, the exposed wafer was heated on a hot plate at 110 ° C. for 1 minute, then allowed to cool and developed using a developing machine (AD-1200 Takizawa Sangyo). Then, Ti and Au were vapor-deposited so that each film thickness might be set to 10 nm with EB vapor deposition machine (SEC-06T-SP Showa Vacuum make). After vapor deposition, the wafer on which Ti and Au were vapor-deposited was placed in an acetone solvent for 30 minutes, and then subjected to an ultrasonic cleaner (VS-D100 manufactured by ASONE) for 3 minutes to remove the resist film. A patterned electrode was produced by these steps. The produced pattern electrode is shown in FIG.

  The obtained pattern electrode 22 was placed on the observation part of the sample stage 16 of the optical microscope, and each electrode 1 to 3 of the pattern electrode 22 was connected to the electrical signal detection part 20 via the current amplifier 24. 50 μl of a culture solution containing Paramecium is dropped from above. Next, 10 μl of 10 mM nickel chloride, which is an anesthetic that stops movement of Paramecium cilia, is dropped. While observing with an optical microscope, the electrode probe 12 was operated using a high performance manipulator (operation unit 14) on the Paramecium that stopped moving, and the electrode probe 12 for voltage application was brought into contact with the surface of the Paramecium. FIG. 7 shows a graph in which the current flowing in response to the voltage applied from the electrode probe 12 at a step of 100 mV is plotted for all the electrodes as in the second embodiment. Each of the electrodes 1 to 3 of the pattern electrode shown in FIG. 7 corresponds to FIG. 8 showing a state in which cells (paramecium) are arranged on each of the electrodes 1 to 3 of the pattern electrode. As can be seen from FIG. 7, a weak current of 10 pA from one living cell can be detected from each electrode 1 to electrode 3 of each pattern electrode, and the current value is reversed depending on the position of the cell. That is, it can be seen that the current distribution of one cell can be measured simultaneously.

Example 4
Carboxylic acid-modified carbon nanotubes were synthesized as follows. 30 mg of multi-walled carbon nanotube powder (purity 90%, average diameter 30 nm, average length 3 μm; manufactured by Science Laboratories) is added to 20 ml of concentrated nitric acid (60% by mass aqueous solution, manufactured by Kanto Chemical), and refluxed at 120 ° C. for 20 hours. Carbon nanotube carboxylic acid was synthesized. After returning the temperature of the solution to room temperature, centrifugation was performed at 5000 rpm for 15 minutes to separate the supernatant and the precipitate. The collected precipitate was dispersed in 10 ml of pure water and centrifuged again at 5000 rpm for 15 minutes to separate the supernatant and the precipitate (one washing operation as described above). This washing operation was further repeated 5 times, and finally the precipitate was collected to obtain carboxylic acid-modified carbon nanotubes.

  0.2 g of the obtained carboxylic acid-modified nanotube was mixed with 10 ml of glycerin (manufactured by Kanto Chemical), 0.2 g of platinum black (manufactured by Wako Pure Chemical Industries), 2 ml of methanol, and 100 μl of concentrated sulfuric acid (98 mass% aqueous solution, manufactured by Kanto Chemical). did.

  The mixed solution was applied to the cross-section of the conductor tip by bringing 1 ml of the mixed solution into contact with the tip of the fine conductor produced in Example 1 using a manipulator. Thereafter, electromagnetic waves were irradiated for 5 seconds in a microwave oven to solidify the mixed solution at the tip. As a result, a microconductor having carbon nanotubes and platinum black exposed only at the tip was produced.

Hydrogen peroxide electrochemical measurement was performed using two of these microconductors as electrodes. As the electrolytic solution, a 0.1 M aqueous solution of potassium chloride (manufactured by Wako Pure Chemical Industries) was used. Using these electrodes, cyclic voltammetry of hydrogen peroxide adjusted to a concentration of 100 pM (= 10 ⁻¹² M) was measured. The measurement results are shown in FIG. As can be seen from FIG. 9, a reduction peak of hydrogen peroxide was observed in the vicinity of −1.5V. Thus, the microconductor produced in Example 1 can also be used for electrochemical measurement, and even when the potential is swept in the range of +3.2 V to -3.2 V, the electrolysis of the solvent does not occur. It was found to have a wide potential window of at least 6.4V.

It is the schematic which shows an example of the cellular electric signal detection apparatus of this invention. It is a block diagram which shows an example of an internal structure of the cellular electric signal detection apparatus of this invention. It is a figure which shows the micro insulation coating metal conductor produced in Example 1, and Fig.3 (a) is a perspective view. FIG. 3B is a side view. In Example 2, it is a figure which shows a mode that the electrode probe for electric current detection was inserted in the inside of a cell (Paramphidae), and the electrode probe for voltage application was made to contact the cell (Paramphidae) surface. 4 is a graph showing current values in response to cell voltages obtained in Example 2. FIG. 6 is a view showing a patterned electrode produced in Example 3. FIG. 6 is a graph showing current values from electrodes 1 to 3 of a pattern electrode obtained in Example 3. It is a figure which shows a mode that the cell (Paramecium) was arrange | positioned to each electrode 1-3 of the pattern electrode obtained in Example 3. FIG. 6 is a graph showing cyclic voltammetry of hydrogen peroxide obtained in Example 4.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Cell electrical signal detection apparatus 12 Electrode probe 14 Operation part 16 Sample stage 16 of optical microscope 16 Sample stage 20 Electrical signal detection part 22 Pattern electrode 24 Current amplifier

Claims (16)

A first step of heating a part of a wire in which a metal material is sealed in a hollow insulator until the insulator is softened;
A second step of stretching the heated portion of the wire and cutting the wire;
A method for producing a finely insulated coated metal conductor, comprising:   2. The method of manufacturing a finely insulated coated metal conductor according to claim 1, wherein the wire is formed by melting the metal material having a melting point lower than that of the hollow insulator and enclosing the metal material in the hollow insulator. Method.   2. The micro-insulation-coated metal conductor according to claim 1, wherein the wire material is obtained by dispersing the metal material in a resin material having a melting point lower than that of the hollow insulator, and encapsulating the wire material in the hollow insulator. Manufacturing method. Furthermore, the cleavage site in cut the wire, and carbon nanotube, a metal, metal oxide, proteins, and a catalyst selected them from carrying carbon pieces, insulating encapsulation material to seal them or their manufacturing method for a micro insulating coated metal conductor according to claim 1, characterized in that it comprises a third step of applying the precursor, the solution containing the. 2. The method for producing a finely insulated coated metal conductor according to claim 1, wherein, in the second step, the wire is cut by stretching so that a major axis of an end surface of a cut portion of the wire becomes 100 nm to 3 μm. .   The said metal material is at least 1 sort (s) selected from low melting-point solder, gallium, aluminum, tin, gold | metal | money, silver, copper, platinum, and iron, The micro insulation coating metal electroconductivity of Claim 1 characterized by the above-mentioned. Body manufacturing method. 2. The method for producing a finely insulated metal conductor according to claim 1, wherein the hollow insulator has a volume resistance value of 10 ⁵ Ωcm or more.   The material of the hollow insulator is at least one selected from glass, quartz, ceramics, Teflon (R), polyimides, and polycarbonates, and the finely insulated coated metal conductive material according to claim 1 Body manufacturing method. A hollow insulator;
An encapsulating material encapsulated in the hollow insulator, wherein the encapsulating material is made of a metal material having a melting point lower than that of the hollow insulator, or the metal material is dispersed and has a melting point higher than that of the hollow insulator. An encapsulant composed of a low resin material;
Comprising
At least one end is exposed to the metal material from the hollow insulator, and the major axis of the end face of the one end is 100 nm to 3 μm.   The finely insulated metal conductor according to claim 9, wherein the one end where the metal material is exposed is tapered.   The said metal material is at least 1 sort (s) selected from low melting-point solder, gallium, aluminum, tin, gold | metal | money, silver, copper, platinum, and iron, The micro insulation coating metal electroconductivity of Claim 9 characterized by the above-mentioned. body. 10. The micro-insulation-coated metal conductor according to claim 9, wherein the hollow insulator has a volume resistance value of 10 ⁵ Ωcm or more.   The material for the hollow insulator is at least one selected from glass, quartz, ceramics, Teflon (R), polyimides, and polycarbonates. conductor. Wherein the said metal material exposed at one end, and a carbon nanotube, a metal, metal oxide, proteins, and a catalyst selected them from carrying carbon piece, an insulating sealing material for sealing them, the The fine insulating coating metal conductor according to claim 9, wherein a mixture comprising the adhering material is adhered. A cell electrical signal detection device comprising a cell electrical signal detection electrode to be brought into contact with a cell, and an electrical signal detection unit for detecting an electrical signal from the cell electrical signal detection electrode,
The micro-insulation-coated metal conductor obtained by the method for producing a micro-insulation-coated metal conductor according to any one of claims 1 to 8, or the electrodes 9 to 14 as the electrode for cell electrical signal detection. A cellular electrical signal detection device using the metal conductor according to any one of the above. As the cell electrical signal detection electrode comprises a plurality of said micro-insulating coating metal conductors, the metal material in the plurality of minute dielectric coated metal conductor according to claim 15, characterized in that the same material Cell electrical signal detector.