JP5108810B2 - Nerve electrode device, method for producing the same, and method for using the same - Google Patents

Description

  The present invention relates to a neural electrode device capable of detecting or inducing electrical and chemical reactions in biological tissue, a method for manufacturing the same, and a method for using the same.

  As a typical method for directly measuring the nerve activity of a biological tissue such as a brain / nerve, there are a method using a microdialysis probe and a method using an electrode. In the former, tissue fluid of a living tissue is collected using a microdialysis probe, and the collected tissue fluid is analyzed to measure a chemical signal of nerve activity of the living tissue. In the latter, an electrical signal of nerve activity of a living tissue is measured using an electrode. In some cases, a chemical solution is injected into a living tissue using a microdialysis probe, or an electrical stimulation is applied to the living tissue using an electrode, and the response of the living tissue to them is measured. In general, a microdialysis probe and an electrode are elements that are independent of each other. Processing such as measurement of a chemical signal using a microdialysis probe and processing such as measurement of an electrical signal using an electrode are performed separately. Done. In such a method, the chemical signal and electrical signal of the same or adjacent living tissue are simultaneously measured, the electrical signal is measured while injecting a chemical solution into the living tissue, or the chemical signal is applied while applying electrical stimulation to the living tissue. It is difficult to measure signals.

  As a rare method, there is a method of measuring both the chemical signal and the electric signal described above using an element in which a needle electrode is bonded to a microdialysis probe (see Non-Patent Document 1). In this method, chemical signals and electrical signals of the same or adjacent living tissue can be measured simultaneously.

  Non-Patent Document 2 discloses a plate-like probe in which an outflow tube for injecting a chemical solution into a nerve tissue and an electrode for measuring an electrical signal of the nerve tissue and performing electrical stimulation to the nerve tissue are integrated. Is disclosed. The opening of the outflow pipe and the electrode are provided on one plate surface of the probe.

Gruss M, Bock J, Braun K., "Haloperidol impairs auditory filial imprinting and modulates monoaminergic neurotransmission in an imprinting-relevant forebrain area of the domestic chick", J Neurochem, Vol. 87 (3), pp. 686-696 (2003 ). Chen J, Wise KD, Hetke JF, Bledsoe SC Jr., "A multichannel neural probe for selective chemical delivery at the cellular level", IEEE Trans Biomed Eng.Vol. 44 (8), pp. 760-769 (1997).

  In order to manufacture an element as described in Non-Patent Document 1, it is necessary to perform alignment between a separately prepared microdialysis probe and a needle electrode and bond them together. However, it is difficult to accurately perform alignment between the physically independent microdialysis probe and the needle electrode. In the element as described in Non-Patent Document 1, the attachment position of the needle electrode with respect to the microdialysis probe is difficult. The accuracy of is low. Therefore, in the case of a configuration in which a plurality of needle electrodes are attached to the microdialysis probe, the positional accuracy between the needle electrodes is low, and an electrical signal cannot be measured with high accuracy. Further, the needle electrode is measured at only one point, and in order to increase the number of electrode channels in the configuration of Non-Patent Document 1, it is necessary to increase the number of needle electrodes adhered to the microdialysis probe. . However, as the number of needle electrodes increases, the volume of the element increases and the degree of invasiveness of the biological tissue that is the measurement target also increases. These problems become more pronounced as the number of needle electrodes attached to the microdialysis probe increases.

  Further, in the configuration in which the opening of the outflow tube and the electrode are arranged on the plate surface of the probe as in Non-Patent Document 2, the outflow direction of the chemical solution and the electrical stimulation / measurement direction by the electrode are limited to the direction perpendicular to the plate surface. , Their freedom is low.

  The present invention has been made in view of the above points, and is intended to collect tissue fluid from a living tissue and / or to inject a chemical solution into the living tissue, to measure an electrical signal of the living tissue, and / or to apply electricity to the living tissue. Providing a technology that can perform stimulation with a single element, improve the degree of freedom and positional accuracy of those directions, and increase the number of electrode channels without increasing the volume. The purpose is to do.

  In the present invention, the nerve electrode device is inserted into a living tissue, and is formed on a tubular tube portion and an outer peripheral surface of the tube portion or a first insulating layer covering the outer peripheral surface of the tube portion. A guide including a metal layer and a second insulating layer made of a photosensitive insulating material that covers a part of the metal layer, and an electrode region where the metal layer is exposed to the outside and a wiring region covered with the second insulating layer There is provided a nerve electrode device having a tube and a fluid mechanism unit that collects tissue fluid from a living tissue and / or injects a chemical solution into the living tissue, and at least a part of the fluid mechanism unit is accommodated inside the guide tube. Provided. Note that at least the second insulating layer and the metal layer are thin films, respectively.

  In this configuration, since the electrode region is provided on the outer peripheral surface side of the tubular tube portion, compared with the configuration in which the electrode is provided only on one side of the plate surface as in the probe of Non-Patent Document 2, the installation position of the electrode region is The degree of freedom is high, and the degree of freedom in measuring the electrical signal and the direction of electrical stimulation is high.

  Moreover, in this invention, an electrode area | region is comprised by covering a part of metal layer formed on the outer peripheral surface of a tube part, or the 1st insulating layer which covers the outer peripheral surface of the said tube part with a 2nd insulating layer. Has been. Such a configuration is a configuration that can be manufactured with higher positional accuracy than a microdialysis probe as in Non-Patent Document 1 in which a needle electrode is bonded.

  Further, in order to increase the number of electrode channels in the configuration of the present invention, it is only necessary to change the pattern of the metal layer or the second insulating layer having a thin film structure, and the volume is hardly increased by this.

  As described above, in the present invention, the collection of the tissue fluid from the living tissue and / or the injection of the chemical solution into the living tissue and the measurement of the electrical signal of the living tissue and / or the electrical stimulation to the living tissue are performed by one element. In addition, the degree of freedom in the direction and the positional accuracy can be improved, and the number of electrode channels can be increased without increasing the volume.

FIG. 1 is a perspective view of the nerve electrode device according to the first embodiment. 2 is a cross-sectional view taken along the line II-II in FIG. 3 is a cross-sectional view taken along the line III-III in FIG. FIG. 4 is a cross-sectional view for explaining the method of manufacturing the nerve electrode device according to the first embodiment. FIG. 5 is a cross-sectional view for explaining the method of manufacturing the nerve electrode device according to the first embodiment. FIG. 6 is a flowchart for explaining the manufacturing method of the nerve electrode device according to the first embodiment. FIG. 7 is a flowchart for explaining the manufacturing method according to the first modification of the first embodiment. It is sectional drawing for demonstrating the modification 2 of 1st Embodiment. FIG. 9 is a perspective view of the nerve electrode device according to the second embodiment. 10 is a cross-sectional view taken along the line IX-IX in FIG. FIGS. 11A to 11D are diagrams illustrating a modification of the guide tube.

Below, after explaining the principle of the present embodiment, the details thereof will be described.
〔principle〕
The nerve electrode device according to the present embodiment includes a tubular tube portion, a metal layer formed on the outer peripheral surface of the tube portion, or a first insulating layer covering the outer peripheral surface of the tube portion, and a part of the metal layer A guide tube including a second insulating layer made of a photosensitive insulating material that covers the fluid, and a fluid mechanism that collects the tissue fluid from the living tissue and / or injects the liquid medicine into the living tissue. The metal layer includes an electrode region exposed to the outside and a wiring region covered with the second insulating layer, and at least a part of the fluid mechanism is accommodated in the guide tube. Further, at least the metal layer and the second insulating layer are thin films. “Thin film” means that the thickness t of one layer is 0 <t <10 μm.

  As described above, in this configuration, the collection of the tissue fluid from the living tissue and / or the injection of the chemical solution into the living tissue and the measurement of the electrical signal of the living tissue and / or the electrical stimulation to the living tissue are performed by one element. In addition, the degree of freedom in the direction and the positional accuracy can be improved, and since the metal layer and the second insulating layer have a thin film structure, the number of electrode channels can be increased without increasing the volume. Can be increased. An example of the fluid mechanism unit is a microdialysis probe that includes a dialysis membrane that is a semipermeable membrane, and that collects tissue fluid from a biological tissue and / or injects a chemical solution into the biological tissue via the dialysis membrane. .

  Preferably, in the present embodiment, the outer peripheral surface of the tube portion or the surface of the first insulating layer covering the outer peripheral surface of the tube portion includes an anchor bottom surface region that is a region exposed to the outside, and the periphery of the anchor bottom surface region is Surrounded by the first insulating layer and / or the second insulating layer. Accordingly, a concave portion (hereinafter referred to as “anchor”) having the anchor bottom surface region as the bottom surface and the first insulating layer and / or the second insulating layer surrounding the anchor bottom surface region as the inner wall surface is formed on the outer peripheral surface of the guide tube. Is formed. The number of anchors may be singular or plural.

  Conventional configurations such as Non-Patent Documents 1 and 2 do not have a structure for stabilizing the position in a living tissue such as an inserted brain. For this reason, in the conventional configurations such as Non-Patent Documents 1 and 2, regardless of the hardness of the material, the movement of the inserted living tissue cannot be followed and a position shift occurs. In this case, the living tissue is damaged or killed by the inserted probe or other element, or the probe or other element is moved out of the measurable or stimulable range. As a result, stable measurement and stimulation are difficult. It was.

  On the other hand, such a problem can be solved by the configuration in which one or more anchors are provided on the surface of the guide tube described above. That is, when the guide tube is inserted to a position where the anchor reaches a living tissue such as the brain and is placed in the living tissue, the living tissue enters the anchor which is a recess. Thereby, the position of the nerve electrode device in the living tissue is stabilized, and the displacement can be prevented. As a result, it is possible to prevent the biological tissue from being damaged or killed by the nerve electrode device, or the nerve electrode device from moving outside the measurement or stimulation possible range, and as a result, stable measurement and stimulation are possible.

  In the present embodiment, preferably, the guide tube constituting the nerve electrode device is separable from the fluid mechanism unit, and the fluid mechanism unit can be inserted into the guide tube from at least one end of the guide tube. The fluid mechanism portion inserted into the inside of the guide tube can be taken out from the one end of the guide tube.

  Non-Patent Documents 1 and 2 and the like are configured to collect a tissue fluid and / or to inject a chemical solution (such as a microdialysis probe), to measure an electrical signal of a biological tissue, and / or to perform electrical stimulation to the biological tissue. The electrode was integrated. Therefore, during measurement or stimulation of living tissue, if the part where tissue fluid is collected and / or injected with chemicals is clogged or malfunctions, the electrode is placed in the living tissue. As such, the malfunctioning part could not be replaced.

  On the other hand, in the configuration in which the guide tube of the present embodiment is separable from the fluid mechanism, the fluid mechanism that collects tissue fluid and / or injects a chemical solution malfunctions during measurement or stimulation of living tissue. Even in the case of falling into a malfunction, the fluid mechanism part that has malfunctioned can be replaced with a new one while the guide tube in which the electrode region is formed is left in the living tissue.

  In addition, in the configuration in which the guide tube can be separated from the fluid mechanism unit, the degree of freedom of the method of performing measurement and stimulation is improved. In this embodiment, the guide tube is inserted into the living tissue, the tissue fluid is collected from the living tissue and / or the chemical liquid is injected into the living tissue using the fluid mechanism unit, and the living body tissue is used using the electrode region as an electrode. Electrical stimulation and / or measurement of electrical signals of living tissue. Here, when the guide tube is inserted into the living tissue, the fluid mechanism is not inserted into the living tissue at the same time, but the guide tube is inserted into the living tissue first, and then inserted into the living tissue. The fluid mechanism portion may be inserted into the guide tube from one end of the guide tube. For example, the fluid mechanism may be inserted into the guide tube only when stimulation or measurement is performed. In such a configuration, the fluid mechanism can be replaced while the guide tube is left in the living tissue. Therefore, it is possible to perform stable measurement and stimulation for a long period of time while properly using a plurality of types of fluid mechanism units and changing the chemical solution to be injected into the living tissue or changing the tissue fluid recovered from the living tissue.

  Further, immediately after the guide tube is inserted into the living tissue, the portion of the living tissue where the guide tube is inserted is not stable. Therefore, after inserting the guide tube into the living tissue, the state may be maintained until the living tissue is stabilized, and the fluid mechanism may be inserted into the guide tube after the living tissue is stabilized. Thereby, the activity of the stable biological tissue can be measured.

Moreover, the nerve electrode apparatus of this form can be manufactured by the following steps, for example.
(a) A step of forming a metal layer on the outer peripheral surface of the tubular tube portion or on the first insulating layer covering the outer peripheral surface of the tube portion.
(b) A step of forming an electrodeposited photoresist layer over the entire surface on which the metal layer is formed.
(c) Using a mask on which a predetermined shape is drawn, the electrodeposition photoresist layer is exposed, the exposed electrodeposition photoresist layer is developed, and the electrodeposition photoresist layer includes an electrode region and a wiring region. Step to shape.
(d) A step of wet etching the metal layer on which the electrodeposited photoresist layer exposed and developed in step (c) is formed.
(e) removing the electrodeposited photoresist layer;
(f) A step of forming a second insulating layer made of a photosensitive insulating material on the entire surface on the metal layer side wet-etched in step (d).
(g) A mask having a predetermined shape is disposed on the second insulating layer, the second insulating layer is exposed, the exposed second insulating layer is developed, and the electrode region is externally covered while covering the wiring region of the metal layer. Processing the second insulating layer into a shape to be exposed to the surface.

  Further, when providing the anchor, in step (g), by removing a part of the second insulating layer, the first insulating layer covering a part of the outer peripheral surface of the tube part or the outer peripheral surface of the tube part. The anchor bottom surface area which is a part of the surface is exposed to the outside, and the first insulating layer and / or the second insulating layer surrounding the anchor bottom surface area is defined as the inner wall surface on the surface of the guide tube. A recessed portion (anchor) is formed.

  In this embodiment, by using the electrodeposition photoresist layer or the second insulating layer made of a photosensitive insulating material, even if the outer peripheral surface of the tube portion is a curved surface or an uneven surface, a desired electrode region is high on the surface. Can be formed with accuracy.

  That is, conventionally, when an electrode for measuring an electrical signal of a living tissue is formed as a thin film, a dry etching process such as plasma etching or reactive ion etching is generally used. However, the dry etching process can be used only when the object to be etched is arranged on a plane. The reason is that the etching amount by the dry etching process is constant with respect to the length of the depth component (a component perpendicular to a certain plane), and the etching object is arranged on a curved surface or an uneven surface. However, it cannot be processed so that the etching amount is uniform on the curved surface or the uneven surface.

  On the other hand, in the manufacturing process of this embodiment, pattern formation is performed by exposure and development without performing a dry etching process. Therefore, even if the outer peripheral surface of the tube portion is a curved surface or a concavo-convex surface, the problem of the dry etching process described above is avoided, and the single or plural electrode regions on the outer peripheral surface with high accuracy of micrometer size. Can be formed at once.

[First Embodiment]
First, a first embodiment of the present invention will be described.

<Configuration>
1 is a perspective view of the nerve electrode device 1 of the first embodiment, FIG. 2 is a cross-sectional view taken along the line II-II in FIG. 1, and FIG. 3 is a cross-sectional view taken along the line III-III in FIG.

  As shown in FIGS. 1 to 3, the nerve electrode device 1 according to the present embodiment includes a cylindrical guide tube 11 and a fluid mechanism unit 12 that collects tissue fluid from a living tissue and / or injects a medical solution into the living tissue. An annular fixing portion 13 having a hollow portion, a fixing cap 14, a connector 15 having a plurality of pins, a cable 16, a ground electrode 17a, and a reference electrode 17b.

[Guide tube 11]
As shown in FIG. 2, the guide tube 11 of this embodiment includes a tubular tube portion 11c, a first insulating layer 11d that covers the outer peripheral surface of the tube portion 11c, and a metal layer formed on the first insulating layer 11d. 11a and a second insulating layer 11e made of a photosensitive insulating material that covers a part of the metal layer 11a. The metal layer 11a includes an electrode region 11aa exposed to the outside and a wiring region 11ab covered with the second insulating layer 11e. As shown in FIGS. 1 and 3, in this embodiment, a plurality of electrode regions 11aa are provided. These electrode regions 11aa include an electrode that performs measurement of an electrical signal of a living tissue and / or electrical stimulation to the living tissue, a ground electrode, and a reference electrode. The electrode regions 11aa, which are electrodes for measuring the electrical signal of the living tissue and / or conducting electrical stimulation to the living tissue, are insulated from each other, and the connector 15 is connected to each other through the wiring regions 11ab and the cables 16 that are electrically insulated from each other. It is electrically connected to each pin. In addition, each electrode region 11aa that is a ground electrode or a reference electrode is also insulated from the other electrode regions 11aa, and is electrically connected to the ground electrode 17a and the reference electrode 17b through the mutually insulated wiring regions 11ab. ing.

  In addition, the shape of the tube part 11c shown by this form is an example, and does not limit this invention. That is, the tube portion 11c is not limited to a cylindrical shape, and may be another cylindrical shape whose cross section is an ellipse or a polygon. Further, the shape, arrangement, and number of the electrode regions 11aa shown in this embodiment are merely examples, and the present invention is not limited thereto. That is, the planar shape of the electrode region 11aa may be any shape such as a circle, an ellipse, or a polygon. In addition, a plurality of electrode regions 11aa may be arranged in the longitudinal direction of the guide tube 11, or a single or a plurality of columns in which a plurality of electrode regions 11aa are arranged in the longitudinal direction may be provided. Further, the plurality of electrode regions 11aa may be arranged so as to circulate around the outer peripheral surface of the guide tube 11 in an annular shape. In addition, a plurality of electrode regions 11aa may be provided, or only one electrode region 11aa may be provided. As described above, in the configuration of the present embodiment, various arrangement modes of the electrode regions 11aa are possible.

  As shown in FIGS. 1 and 2, the outer peripheral surface of the tube portion 11 c includes an anchor bottom surface region 11 ba that is a region exposed to the outside. The periphery of the anchor bottom region 11ba is surrounded by the first insulating layer 11d and the second insulating layer 11e. The anchor bottom region 11ba is the bottom surface, and the first insulating layer 11d and the second insulating layer 11e surrounding the anchor bottom region 11ba are surrounded by the anchor bottom region 11ba. An anchor 11b is formed as a recess having an inner wall surface 11bb.

  In addition, the shape, arrangement | positioning, and number of the anchor bottom face area | region 11ba shown by this form are examples, and do not limit this invention. That is, the anchor bottom region 11ba may have any shape such as a circle, an ellipse, or a polygon. Further, a plurality of anchors 11b may be arranged in the longitudinal direction of the guide tube 11, or a single or a plurality of rows in which a plurality of anchors 11b are arranged in the longitudinal direction may be provided. Further, the plurality of anchors 11b may be arranged so as to circulate around the outer peripheral surface of the guide tube 11 in an annular shape. A plurality of anchors 11b may be provided, or only one anchor 11b may be provided. Thus, with the configuration of the present embodiment, various arrangement modes of the anchor 11b are possible. Or the structure which does not provide the anchor 11b may be sufficient.

Examples of the material of the metal layer 11a include platinum (Pt), gold (Au), nitrousable titanium (TiO ₂ ), silver oxide (Ag ₂ O), tungsten (W), tin-added indium oxide (Indium Tin Oxide). ), Tin oxide (SnO, SnO ₂ , SnO ₃ ), chromium (Cr), copper (Cu), nickel (Ni), aluminum (Al), and the like. Among these, platinum and gold that are easy to finely process, have high conductivity, and are flexible are desirable.

  Examples of the photosensitive insulating material constituting the second insulating layer 11e include photosensitive polyimide, photosensitive polyamide, photosensitive polyester, photosensitive benzocyclobutene, photosensitive parylene, photosensitive epoxy, and photosensitive acrylate. . Among these, it is more desirable to use a photosensitive polyimide that can be easily processed. The photosensitive insulating material to be used is desirably a material that has a small adverse effect on the living body, has flexibility to follow the deformation of the guide tube, and can be processed into a required film thickness. An example of such a photosensitive insulating material is “Durimide® 7510” manufactured by Fuji Film, which is a kind of photosensitive polyimide.

  Moreover, it is desirable that the first insulating layer 11 is also made of the same photosensitive insulating material as that of the second insulating layer 11e from the viewpoint of efficiency of the manufacturing process. However, when fine processing of the first insulating layer 11 is not necessary, the first insulating layer 11 may be made of another insulating material. For example, the first insulating layer 11 may be configured using a thin film and a biocompatible material (for example, parylene).

  Examples of the material of the tube portion 11c are conductors such as stainless steel, glass such as borosilicate glass and aluminosilicate glass, and insulators such as ceramic such as alumina and mullite.

[Fluid mechanism 12]
As shown in FIG. 3, the fluid mechanism unit 12 of this embodiment includes a dialysis membrane 12a that is a semipermeable membrane, a supply pipe 12b that supplies a reflux solution or a chemical solution to one surface side of the dialysis membrane 12a, It has a return tube 12c that collects the chemical fluid and the tissue fluid collected from the biological tissue via the dialysis membrane 12a. In this embodiment, a dialysis membrane 12a is attached to one end of the guide tube 11, and a reflux solution or a chemical solution is supplied into the guide tube 11 by a supply tube 12b inserted into the other end of the guide tube 11, The reflux liquid, the drug solution, and the tissue fluid inside the guide tube 11 are collected by the return tube 12c inserted at the same end. Thereby, the dialysis membrane 12a, the supply tube 12b, the return tube 12c, and the guide tube 11 function as a microdialysis probe. The microdialysis probe utilizes the property that the liquid separated through the dialysis membrane diffuses in the direction of low concentration gradient, and collects the tissue fluid from the biological tissue and the chemical solution to the biological tissue through the dialysis membrane. Injection. For details, see, for example, Reference 1 “Sugimoto A, Aikawa Y, Kobayashi R, Kurosawa M,“ Responses of hepatic glucose output to noxious mechanical stimulation of the skin in anaesthetized rats ”, Auton Neurosci, vol. 102, No. 1 -2, pp. 45-53 (2002). Although the present embodiment shows an example in which the fluid mechanism unit 12 constitutes a microdialysis probe, the fluid mechanism unit 12 collects tissue fluid from a living tissue and / or injects a drug solution into the living tissue by another configuration. It may be what performs. For example, the fluid mechanism unit 12 may be an injection needle of a syringe that sucks tissue fluid from a biological tissue or injects a chemical solution into the biological tissue.

[Arrangement]
A dialysis membrane 12a is fixed to the opening 11g at one end of the guide tube 11, and the opening 11g is covered with the dialysis membrane 12a. Further, one end sides of the supply pipe 12b and the return pipe 12c are inserted into the guide pipe 11 from the opening 11f at the other end, respectively, and are fixed to the opening 11f side of the guide pipe 11 by the fixing cap 14. Further, the ground electrode 17a, the reference electrode 17b, and the cable 16 connected to the wiring region 11ab as described above are connected to the outer peripheral side surface of the guide tube 11 on the opening 11f side, and the connector 15 is connected to the other end of the cable 16. Is connected. Further, the guide tube 11 is inserted into the hollow portion of the annular fixing portion 13, and the inner wall surface of the hollow portion of the fixing portion 13 is fixed to the outer peripheral surface of the guide tube 11.

<Manufacturing method>
4 and 5 are cross-sectional views for explaining the manufacturing method of the nerve electrode device 1 according to the first embodiment, and FIG. 6 is a flowchart for explaining the manufacturing method. 4 shows an example in the case of using a negative photosensitive insulating material and an electrodeposited photoresist, and FIG. 5 shows an example in the case of using a positive photosensitive insulating material and an electrodeposited photoresist. 4 and 5, the object to be processed is arranged on a plane in FIG. 4 and FIG. 5, but the object to be processed may be arranged on a curved surface or an uneven surface. The manufacturing process of the nerve electrode device 1 of this embodiment is as follows.

  [S101] The first insulating layer 11d is formed on the outer peripheral surface of the tube portion 11c (FIGS. 4A to 4C and FIGS. 5A to 5C). In the example shown in FIGS. 4A to 4C and FIGS. 5A to 5C, the first insulating layer 11d is made of a photosensitive insulating material. In this example, first, the first insulating layer 11d is formed on the entire outer peripheral surface of the tube portion 11c (FIGS. 4A and 5A). Next, the first insulating layer 11d is exposed using the mask 101 on which the shape for removing the first insulating layer 11d located in the anchor bottom region 11ba is drawn, and the exposed first insulating layer 11d is developed. (FIG. 4 (b), FIG. 5 (b)). As a result, the first insulating layer 11d located in the anchor bottom region 11ba is removed (FIGS. 4C and 5C).

  [S102] A metal layer 11a is formed on the first insulating layer 11d covering the outer peripheral surface of the tube portion 11c (FIGS. 4D and 5D).

  [S103] An electrodeposited photoresist layer 102 is formed on the entire surface on which the metal layer 11a is formed in step S102 (FIGS. 4E and 5E). An example of the electrodeposition photoresist constituting the electrodeposition photoresist layer 102 is “Elecoat EU-XC series” manufactured by Shimizu Corporation.

  [S104] Using the mask 103 on which a predetermined shape is drawn, the electrodeposited photoresist layer 102 is exposed, the exposed electrodeposited photoresist layer 102 is developed, and the electrodeposited photoresist layer 102 is wired to the electrode region 11aa. It is processed into a shape including the region 11ab (FIGS. 4 (f) (g) and 5 (f) (g)). Examples of the shape including the electrode region 11aa and the wiring region 11ab include a shape including the electrode region 11aa and the wiring region 11ab, a shape including the electrode region 11aa, the wiring region 11ab, and an element region such as a resistor and a coil. .

  [S105] The metal layer 11a on which the electrodeposited photoresist layer 102 exposed and developed in step S104 is wet-etched (FIGS. 4H and 5H). Thereby, the metal layer 11a is processed into a shape including the electrode region 11aa and the wiring region 11ab.

  [S106] The electrodeposited photoresist layer 102 is removed (FIGS. 4 (i) and 5 (i)).

  [S107] A second insulating layer 11e made of a photosensitive insulating material is formed on the entire surface on the metal layer 11a side wet-etched in step S105 (FIGS. 4 (j) and 5 (j)).

  [S108] A mask 104 having a predetermined shape is disposed on the second insulating layer 11e, the second insulating layer 11e is exposed, the exposed second insulating layer 11e is developed, and the wiring region 11ab of the metal layer 11a is formed. The second insulating layer 11e is processed into a shape that exposes the electrode region 11aa to the outside while covering it, and further exposes the anchor bottom region 11ba to the outside (FIGS. 4 (k) (l), 5 (k) (l)). ). In this way, by removing a part of the second insulating layer 11e, the electrode region 11aa of the metal layer 11a and the anchor bottom region 11ba on the outer peripheral surface of the tube portion 11c are exposed to the outside. As a result, the anchor 11b, which is a recess having an anchor bottom surface region 11ba as a bottom surface and a first insulating layer 11d and a second insulating layer 11e surrounding the anchor bottom surface region 11ba as an inner wall surface 11bb on the outer peripheral surface of the guide tube 11c, The electrode region 11aa is formed.

  A dialysis membrane 12a is fixed to one end of the guide tube 11 generated as described above. Further, the supply pipe 12 b and the return pipe 12 c are inserted into the guide pipe 11 from the other end, and are fixed to the guide pipe 11 by the fixing cap 14. Further, the cable 16 connected to the connector 15, the ground electrode 17 a and the reference electrode 17 b are connected to each wiring region 11 ab that is electrically connected to each electrode region 11 aa independently, and the fixing portion 13 is attached to the guide tube 11. .

<How to use>
Next, the usage method of the nerve electrode apparatus 1 of this form is demonstrated.
First, the guide tube 11 of the nerve electrode device 1 is inserted into a biological tissue such as the brain of an animal (for example, a human or an animal other than a human) and fixed by the fixing unit 13. In this embodiment, since the fluid mechanism unit 12 including the dialysis membrane 12 and the like is fixed to the guide tube 11, the dialysis membrane 12 is also inserted into the living tissue. In this embodiment, the guide tube 11 is inserted into the living tissue until a position where at least a part of the anchor 11b formed on the surface of the guide tube 11 reaches the living tissue. As a result, the living tissue enters the anchor 11b which is a recess, and the position of the nerve electrode device 1 in the living tissue is stabilized. In this state, the fluid mechanism unit 12 including the dialysis membrane 12 or the like is used to collect the tissue fluid from the living tissue and / or inject the drug solution into the living tissue. In addition, the electrode region 11aa is used as an electrode to perform electrical stimulation to the living tissue and / or measurement of an electrical signal of the living tissue.

[Variation 1 of the first embodiment]
When the tube portion 11c is formed of an insulator material, the above-described processing in step S101 is not necessary. FIG. 7 is a flowchart for explaining the manufacturing method in this case. In this case, the guide tube is manufactured by the following manufacturing process without executing Step S101.

  [S202] The metal layer 11a is formed on the outer peripheral surface of the tube portion 11c.

  [S203] An electrodeposited photoresist layer 102 is formed on the entire surface on which the metal layer 11a is formed in step S202.

  [S104 to S108] Thereafter, the processes of S104 to S108 are performed.

  In the first modification of the first embodiment, the first insulating layer 11d does not exist. Therefore, a part of the outer peripheral surface of the tube portion 11c becomes the anchor bottom surface region 11ba. In the case of this example, the anchor 11b is a recess having the anchor bottom region 11ba as a bottom surface and the second insulating layer 11e surrounding the anchor bottom region 11ba as an inner wall surface.

[Modification 2 of the first embodiment]
The anchor bottom region 11ba of the first embodiment was a part of the outer peripheral surface of the tube portion 11c. However, as illustrated in FIG. 8, a part of the first insulating layer 11d covering the outer peripheral surface of the tube portion 11c may be the anchor bottom surface region 11ba. In the case of this example, the anchor 11b is a recess having the anchor bottom region 11ba as a bottom surface and the second insulating layer 11e surrounding the anchor bottom region 11ba as an inner wall surface. In FIG. 8, the same reference numerals as those in the first embodiment are used for the same parts as those in the first embodiment.

[Second Embodiment]
The second embodiment is a modification of the first embodiment. The guide tube of this embodiment is separable from the fluid mechanism portion, the fluid mechanism portion can be inserted into the guide tube from at least one end of the guide tube, and the fluid mechanism portion inserted into the guide tube is It can be taken out from the one end of the guide tube. Below, it demonstrates centering around difference with 1st Embodiment, and abbreviate | omits description about the matter which is common in 1st Embodiment.

<Configuration>
FIG. 9 is a perspective view of the nerve electrode device 2 according to the second embodiment, and FIG. 10 is a cross-sectional view taken along the line IX-IX in FIG. In FIG. 9, the same reference numerals as those in the first embodiment are used for the same portions as those in the first embodiment.

  As shown in FIGS. 9 and 10, the nerve electrode device 2 of the present embodiment includes a cylindrical guide tube 11, a fixing portion 13, a fixing cap 14, and a plurality of the same as in the first embodiment or the modification thereof. A connector 15 having pins, a cable 16, a ground electrode 17a, and a reference electrode 17b are provided. Further, the nerve electrode device 2 of the present embodiment has a fluid mechanism portion 22 that can be separated from the guide tube 11 instead of the fluid mechanism portion 12 of the first embodiment.

  The fluid mechanism unit 22 of this embodiment is a normal microdialysis probe that collects tissue fluid from a biological tissue and / or injects a medical fluid into the biological tissue. The fluid mechanism 22 includes a dialysis membrane 12 a, a supply tube 12 b, a return tube 12 c, a fixed cap 14, and a tubular tube portion 22 d having an outer diameter smaller than the inner diameter of the guide tube 11. The dialysis membrane 12a is fixed to the opening 22da at one end of the tube portion 22d, and the opening 22da is covered with the dialysis membrane 12a. Further, one end sides of the supply pipe 12b and the return pipe 12c are respectively inserted into the tube part 22d from the opening part 22db at the other end, and they are fixed to the opening part 22db side of the tube part 22d by the fixing cap 14. The tube portion 22d is made of the same material as that of the guide tube 11, for example.

  The end of the fluid mechanism 22 on the side where the dialysis membrane 12 a is provided can be inserted into the guide tube 11 through the opening 11 f of the guide tube 11. When the fluid mechanism portion 22 is inserted into the guide tube 11, the dialysis membrane 12 a of the fluid mechanism portion 22 protrudes from the opening portion 11 g of the guide tube 11 to the outside. Thereby, the collection | recovery of the tissue fluid from a biological tissue and / or the injection | pouring of a chemical | medical solution to a biological tissue through the dialysis membrane 12a is attained. In addition, if the collection | recovery of the tissue fluid from a biological tissue and / or the injection | pouring of a chemical | medical solution to a biological tissue are possible via the dialysis membrane 12a, the dialysis membrane 12a of the fluid mechanism part 22 does not necessarily pass from the opening part 11g of the guide tube 11. It does not need to protrude outside, and may remain disposed inside the guide tube 11. Further, the fluid mechanism 22 inserted into the guide tube 11 in this way can be taken out from the opening 11 f of the guide tube 11.

<How to use>
Next, the usage method of the nerve electrode apparatus 2 of this form is demonstrated.
First, the guide tube 11 of the nerve electrode device 2 is inserted into a biological tissue such as a brain of an animal (for example, a human or an animal other than a human) and fixed by the fixing unit 13. At this time, the fluid mechanism 22 is not inserted into the guide tube 11. In this embodiment, the guide tube 11 is inserted into the living tissue until a position where at least a part of the anchor 11b formed on the surface of the guide tube 11 reaches the living tissue. As a result, the living tissue enters the anchor 11b, which is a recess, and the position of the guide tube 11 in the living tissue is stabilized. Then, after waiting for the living tissue to stabilize as necessary, the dialysis membrane 12a side of the fluid mechanism portion 22 is inserted into the guide tube 11 from the opening 11f of the guide tube 11 inserted into the living tissue. . In this state, the fluid mechanism 22 is used to collect the tissue fluid from the living tissue and / or inject the chemical solution into the living tissue. In addition, the electrode region 11aa is used as an electrode to perform electrical stimulation to the living tissue and / or measurement of an electrical signal of the living tissue. In addition, after collecting the tissue fluid from the living tissue and / or injecting the chemical solution into the living tissue, the fluid mechanism unit 22 may be taken out from the opening 11f side of the guide tube 11, or another Another fluid mechanism 22 capable of collecting tissue fluid or injecting another drug solution may be inserted into the guide tube 11 from the opening 11f side to continue measurement and stimulation of the biological tissue.

[Modification 1 of Second Embodiment]
In the second embodiment, the fluid mechanism 22 is a microdialysis probe. However, the fluid mechanism unit 22 may be configured to collect tissue fluid from the living tissue and / or inject a chemical solution into the living tissue by another configuration. For example, the fluid mechanism unit 22 may be an injection needle of a syringe that sucks tissue fluid from a living tissue or injects a drug solution into the living tissue.

[Other variations]
The present invention is not limited to the embodiment described above.
FIGS. 11A to 11D are diagrams illustrating a modification of the guide tube. The guide tube 31 illustrated in FIG. 11A includes an electrode region 11aa similar to that in the first and second embodiments, but is an example in which the arrangement of the anchor 11b is different. The anchor 11b in this example is arranged so as to circulate around the outer periphery of the guide tube 31 in a ring shape, and the anchor 11b arranged in this way is configured in two stages. 11B and 11C, one end of the guide tube 41 is cut obliquely with respect to the longitudinal direction of the guide tube 41. Thereby, the cut end of the guide tube 41 is sharpened, and the guide tube 41 can be easily inserted into the living tissue. The guide tube 41 illustrated in FIGS. 11B and 11C does not include the anchor 11b, but the guide tube 41 may include the anchor 11b. Further, the guide tube 51 illustrated in FIG. 11D is configured with a window portion 51a that is a hole penetrating a part of the outer peripheral side surface on one end side. When such a guide tube 51 is inserted into a living tissue, the tissue fluid can be taken into the guide tube 51 through this window portion 51 a or the drug solution can be discharged to the outside of the guide tube 51. In this case, the dialysis membrane of the fluid mechanism portion is disposed in the vicinity of the window portion 51a.

  In addition, a metal layer or an insulating layer may be formed in multiple layers on the outer peripheral surface of the tube portion. Thereby, a wiring layer can be arrange | positioned with high density.

  Needless to say, other modifications are possible without departing from the spirit of the present invention.

  The present invention can be used, for example, in the field of detecting or inducing both electrical and chemical reactions in living tissue.

1, 2 Neural electrode device

Claims (9)

A nerve electrode device inserted into a living tissue,
A photosensitive insulating material that covers a cylindrical tube portion, a metal layer formed on the outer peripheral surface of the tube portion, or a first insulating layer that covers the outer peripheral surface of the tube portion, and a part of the metal layer A guide tube including a second insulating layer comprising:
A fluid mechanism that collects tissue fluid from a biological tissue and / or injects a medical fluid into the biological tissue,
The metal layer includes an electrode region exposed to the outside and a wiring region covered with the second insulating layer,
Inside the guide tube, at least a part of the fluid mechanism is stored,
At least the second insulating layer and the metal layer are thin films, respectively.
A nerve electrode device characterized by that. The neural electrode device according to claim 1, wherein
The outer peripheral surface of the tube portion or the surface of the first insulating layer covering the outer peripheral surface of the tube portion includes an anchor bottom surface region that is an externally exposed region, and the periphery of the anchor bottom surface region is the first insulating layer. And / or surrounded by the second insulating layer, whereby the anchor bottom surface region is a bottom surface on the outer peripheral surface of the guide tube, and the first insulating layer and / or the second surrounding the periphery of the anchor bottom surface region. A recess having an insulating layer as an inner wall surface is formed,
A nerve electrode device characterized by that. The nerve electrode device according to claim 1 or 2,
The guide tube is separable from the fluid mechanism;
The fluid mechanism portion can be inserted into the guide tube from at least one end of the guide tube, and the fluid mechanism portion inserted into the guide tube can be taken out from the one end of the guide tube. ,
A nerve electrode device characterized by that. The nerve electrode device according to any one of claims 1 to 3,
The fluid mechanism section includes a dialysis membrane that is a semipermeable membrane, and is a microdialysis probe that collects tissue fluid from a biological tissue and / or injects a medical fluid into the biological tissue via the dialysis membrane.
A nerve electrode device characterized by that. (a) forming a metal layer on the outer peripheral surface of the tubular tube portion or on the first insulating layer covering the outer peripheral surface of the tube portion;
(b) forming an electrodeposited photoresist layer over the entire surface on which the metal layer is formed;
(c) using a mask on which a predetermined shape is drawn, exposing the electrodeposited photoresist layer, developing the exposed electrodeposited photoresist layer, and forming the electrodeposited photoresist layer into an electrode region and a wiring region; Processing to a shape including
(d) wet etching the metal layer formed with the electrodeposited photoresist layer exposed and developed in step (c);
(e) removing the electrodeposited photoresist layer;
(f) forming a second insulating layer made of a photosensitive insulating material over the entire surface on the metal layer side wet-etched in step (d);
(g) A mask having a predetermined shape is disposed on the second insulating layer, the second insulating layer is exposed, the exposed second insulating layer is developed, and the wiring region of the metal layer is covered. Processing the second insulating layer into a shape that exposes the electrode region to the outside;
A method of manufacturing a nerve electrode device having A manufacturing method according to claim 4 or 5, wherein
In the step (g), a part of the outer peripheral surface of the tube part or a part of the surface of the first insulating layer covering the outer peripheral surface of the tube part is removed by removing a part of the second insulating layer. A certain anchor bottom region is exposed to the outside, and thereby the first insulating layer and / or the second insulating layer surrounding the periphery of the anchor bottom region on the outer peripheral surface of the guide tube. Including a step of forming a recess having an inner wall surface
The manufacturing method characterized by the above-mentioned. (a) a tubular tube portion, a metal layer formed on the outer peripheral surface of the tube portion or on the first insulating layer covering the outer peripheral surface of the tube portion, and a photosensitive material covering a part of the metal layer A guide tube including an electrode region exposed to the outside and a wiring region covered with the second insulating layer. The guide tube includes a second insulating layer made of a conductive insulating material. Inserting into living tissue; and
(b) At least a part of the fluid is stored in the guide tube and collects the tissue fluid from the living tissue and / or injects the medicinal solution into the living tissue. / Or injecting a drug solution into the living tissue;
(c) using the electrode region as an electrode, performing electrical stimulation to the living tissue and / or measuring an electrical signal of the living tissue;
A method of using a neural electrode device having The method of use of claim 7, comprising:
Step (a) includes
(a-1) inserting the guide tube into the living tissue;
(a-2) including inserting the fluid mechanism portion into the guide tube from one end of the guide tube inserted into the living tissue,
Usage characterized by that. Use of claim 7 or 8, comprising
The outer peripheral surface of the tube portion or the surface of the first insulating layer covering the outer peripheral surface of the tube portion includes an anchor bottom surface region that is an externally exposed region, and the periphery of the anchor bottom surface region is the first insulating layer. And / or surrounded by the second insulating layer, whereby the outer peripheral surface of the guide tube has the anchor bottom surface region as a bottom surface and surrounds the anchor bottom surface region and / or the first insulating layer and / or the first insulating layer. 2 A recess having an insulating wall as an inner wall surface is formed,
The step (a-1) is a step of inserting the guide tube into the living tissue until a recess formed on the surface of the guide tube reaches the living tissue.
Usage characterized by that.

Images