JP4878633B2 - Flexible nerve probe - Google Patents

Description

  The present invention relates to a probe for measuring a weak electrical signal flowing through a nervous system in a living body and inputting a weak electrical signal to the nervous system, and more particularly to a multi-channel probe using a flexible substrate.

  A probe that inserts an electrode needle into a flexible biological tissue such as the brain or nerve bundle and measures information on the nervous system and inputs information to the nervous system is a probe of R.U. A. Published by Norman (see Non-Patent Document 1). This nerve electrode is known as a Utah sword mountain type electrode because it has a large number of silicon electrode needles integrally planted on a silicon substrate, and has an appearance similar to that of sword mountain. Also, K.D.Wise of the University of Michigan in the United States has announced a Kenyama electrode in which a large number of probes provided separately from a substrate are combined on a silicon substrate (see Non-Patent Document 2).

  In addition, a probe having a plurality of flexible electrode needles has been published (see Non-Patent Document 3).

IEEE Transactions on Biomedical Engineering Vol.38, No.8, 1991 (p. 758-768, Fig. 7) IEEE Transactions on Biomedical Engineering Vol. 41, No. 12 1994 (1136 to 1146, Fig. 2) IEEE Proceeding of the 14th International Conference on Micro Electro Mechanical Systems (Proceeding of the 14th IEEE International Conference on Micro Mechanical Systems) Proceedings (pages 216-219, Fig. 4)

  However, since these probes have an electrode needle made of a hard material such as silicon on a substrate made of a hard material such as silicon, the electrode needle is attached to a flexible living tissue such as a brain or a nerve bundle. When the needle is inserted and embedded, it cannot be matched to the shape of the living body part and cannot follow the movement, so that it is difficult not only to align the measurement point of the electrode needle with the target nerve tissue but also to damage the living tissue. Or, there was a problem that stable measurement and stimulation could not be performed for a long time.

  Moreover, the probe having a flexible electrode has a problem that three-dimensional measurement cannot be performed.

  Furthermore, some conventional probes are known in which a plurality of measurement points are arranged at the tip of the electrode needle to enable three-dimensional measurement and stimulation in the nerve tissue. It was cumbersome and not suitable for industrial production.

  Accordingly, the present invention provides a multichannel flexible neuroprobe that improves the above-described problems of the conventional nerve electrode, includes a flexible substrate, enables three-dimensional measurement of nerve tissue, and is easy to manufacture. It is intended to do.

The multichannel flexible neuroprobe of the present invention is sandwiched between a pair of flexible insulating substrates made of a polyparaxylylene polymer, and a plurality of probe conductors erected at a predetermined angle with respect to the surfaces of these insulating substrates. A probe electrode formed by the above, and an electrical wiring connected to an end portion of the probe electrode on the insulating substrate surface side and sandwiched between a pair of flexible insulating substrates that are also made of polyparaxylylene polymer, and A recording pad formed so as to expose a part of each probe conductor by providing a through hole in an insulating substrate that sandwiches the probe conductor at different positions of a plurality of probe conductors forming a probe electrode. It is characterized by this.

  Furthermore, in the multichannel flexible neuroprobe of the present invention, a plurality of the probe electrodes are provided on the flexible insulating substrate.

  According to the present invention, it is possible to provide an easy-to-manufacture multi-channel flexible nerve probe that includes a flexible substrate and enables measurement of a three-dimensional nerve tissue.

It is a perspective view which shows the principal part structure of the multichannel type flexible nerve probe of this invention. FIG. 2 is an enlarged plan view showing a part of FIG. It is process drawing which shows the manufacturing method of the multichannel type flexible nerve probe shown in FIG. It is process drawing which shows the manufacturing method of the multichannel type flexible nerve probe shown in FIG. It is process drawing which shows the manufacturing method of the multichannel type flexible nerve probe shown in FIG. 1, and (h) shows the result of having measured the change of the bending angle of the probe electrode when the intensity | strength of the magnetic field H is changed. It is a graph. It is a perspective view which shows the whole structure of the manufactured multichannel type flexible nerve probe. It is process drawing which shows the other manufacturing method of the multichannel type flexible nerve probe shown in FIG.

  Hereinafter, embodiments of the multi-channel flexible nerve probe of the present invention will be described with reference to the drawings.

  FIG. 1 is a perspective view showing a main part structure of a multi-channel type flexible nerve probe of the present invention, and FIG. 2 is a plan view showing an enlarged part thereof. As shown in FIG. 1, a plurality of, for example, six plate-like probe electrodes 12 are formed in the direction perpendicular to the substrate surface at the end of a strip-like flexible insulating substrate 11. The flexible insulating substrate 11 is made of, for example, a polyimide thin film having a thickness of about 10 microns. As shown in FIG. 2, the plate-like probe electrode 12 has three wiring conductors 13, 14, and 15 along the longitudinal direction in an elongated plate-like flexible insulating substrate 11-1 with a sharp tip. They are arranged almost in parallel. Here, the flexible insulating substrate 11-1 is formed by separating a part of the insulating substrate 11. The three probe conductors 13, 14, and 15 are arranged in parallel along the longitudinal direction of the plate-like probe electrode 12, and their tips end at different positions. In addition, recording pads 13-1, 14-1, and 15-1 for transmitting and receiving nerve information in the living body are formed at the respective distal end portions. These recording pads 13-1, 14-1, and 15-1 are minute through holes formed in the polyimide thin film constituting the insulating substrate 11-1, and three probe conductors are formed through these through holes. A part of 13, 14, 15 is exposed. Further, electrical wirings 16 are connected to the three probe conductors 13, 14, and 15, respectively, and these wirings 16 are opposite to the end portions on which the probes 12 are formed on the strip-shaped flexible insulating substrate 11. It is extended toward the end of the.

  As described above, the multi-channel flexible neuroprobe according to an embodiment of the present invention has a plurality of probes 12 formed in a vertical direction on a flexible insulating substrate 11, and each probe 12 has a different height in the longitudinal direction. A plurality of signal detection / recording recording pads 13-1, 14-1, and 15-1 are formed at this position. Therefore, by inserting this multi-channel flexible neuroprobe into a living body measurement site, the entire substrate 11 provided with the probe electrode 12 can be brought into close contact with the surface shape of the living body, and the movement of the living body. Since the probe electrode 12 can be deformed according to the above, the position of the probe can always be matched with the position of the nerve tissue to be measured. In addition, according to such a multi-channel flexible neural probe, it is possible to measure two-dimensional nerve information of a living body, and also measure nerve information at different positions and depths of a living body. Neural information can be measured.

  3 to 5 are process diagrams showing a method for manufacturing the multi-channel flexible nerve probe. First, as shown in FIG. 3A, a Si substrate 21 which is a semiconductor substrate is prepared. The Si substrate 21 is a generally rectangular substrate having a thickness of about 200 to 250 μm, but only one end portion in the length direction is shown in FIGS. 3 to 5. On the surface of the Si substrate 21, a Ni layer 22, which is a magnetic material having a thickness of about 3 μm, is formed by patterning in the shape of an elongated electrode needle having a pointed tip by electrodeposition. Next, as shown in FIG. 3B, a polyimide resin is applied to the entire surface of the Si substrate 21 by spin coating. The applied polyimide resin is dried to form a first polyimide resin layer 23 having a thickness of about 10 μm. Titanium (Ti) and aluminum (Al) are sequentially laminated on the entire surface of the polyimide resin layer 23 by vacuum vapor deposition to form a metal layer 24. These metal layers 24 are patterned by wet etching to form six probe electrodes 12 and electrical wirings 16 connected thereto. Here, each of the six probe electrodes 12 is composed of three probe conductors 13, 14, 15 as shown in FIG. As shown in FIG. 3C, the second layer polyimide is formed on the entire surface of the Si substrate 21 including the surfaces of the six probe electrodes 12 thus formed and the electrical wirings 16 connected thereto. The resin layer 23 ′ is again formed by spin coating to a thickness of about 10 μm.

Next, as shown in FIG. 4D, the first and second polyimide resin layers 23 and 23 'are patterned into a predetermined shape by oxygen (O ₂ ) plasma etching. That is, the first and second polyimide resin layers 23 and 23 ′ other than the portion where the six probe electrodes 12 and the electrical wiring 16 connected thereto are formed are removed, and the six probe electrodes are removed. Cuts are formed in the polyimide resin layers 23 and 23 ′ around 12 except for the base portion. Similarly, through-holes 25 are formed at the tip portions of the three pad conductors 13, 14, 15 constituting each of the six probe electrodes 12 by oxygen plasma. These through holes 25 are formed in the polyimide resin 23 'at positions corresponding to the recording pads 13-1, 14-1 and 15-1 shown in FIG. These through holes 25 are formed so that the probe conductors 13, 14, 15 come into contact with the nervous system in the living body when the probe electrode 12 is inserted into the living body.

In this oxygen plasma etching process, although not shown, an aluminum layer disposed on the surface of the second layer polyimide resin 23 ′ covering the metal layer 24 is used as a mask. That is, this mask is formed by patterning an aluminum layer vacuum-deposited on the entire surface of the second layer polyimide resin 23 'by photolithography. In this mask pattern, a window is formed in a portion where the first layer and the second polyimide resin layers 23 and 23 'are removed, and etching is performed by irradiating oxygen plasma through the window. This aluminum layer is removed by an etching solution containing H ₃ PO ₄ , HNO ₃ , CH ₃ COOH and H ₂ O in a ratio of 10: 1: 1: 2. Since this etching solution does not damage the titanium layer, the aluminum layer constituting the metal layer 24 constituting the probe conductors 13, 14, 15 and the electrical wiring 16 connected thereto is not removed by this etching.

Next, as shown in FIG. 4E, all the Si substrates 21 including both side portions not covered with the polyimide resin 23 are removed by deep reactive ion etching (DRIE). In DRIE, etching is performed with a thickness of about 20 μm from the back surface of the Si substrate 21, and then etching is performed from the front surface side. Next, as shown in FIG. 4F, the Si substrate 21 is removed from the back side by isotropic etching using XeF ₂ gas. As a result, a probe having a planar structure in which the probe electrode 12 and the electrical wiring 16 connected thereto are sandwiched by the polyimide resins 23 and 23 'is formed. That is, the polyimide resins 23 and 23 ′ sandwich the probe electrode 12 and the electrical wiring 16 connected thereto from the front and back surfaces to constitute a flexible insulating substrate 26.

  When a magnetic field H perpendicular to the surface is applied to the probe having a planar structure configured as described above, the Ni layer 22 which is a magnetic material formed on the back surface of the six probe electrodes 12 receives a magnetic force, As shown in FIG. 5G, the six probe electrodes 12 stand upright on the insulating substrate 26 all at once.

  FIG. 5H is a graph showing the results of measuring the change in the bending angle of the probe electrode 12 when the strength of the magnetic field H is changed. From the figure, it can be seen that the film can be bent to approximately 90 degrees by applying a magnetic field of about 400 mT.

  FIG. 6 is a perspective view showing the overall configuration of the multi-channel flexible nerve probe manufactured as described above. This multi-channel flexible neuroprobe is formed in an elongated strip shape in which six probe electrodes 12 and electrical wirings 16 connected thereto are sandwiched between polyimide resins 23 and 23 '. The electrical wiring 16 is connected to a substantially rectangular terminal pad portion 27 provided on the side opposite to the probe electrode 12. Three terminal pad portions 27 are provided for each of the six probe electrodes 12, and a total of 18 terminal pads 27-1, 27-2,..., 27- correspond to each of the 18 recording pads. 18 are provided, and corresponding recording pads and terminal pads are connected to each other by electrical wiring 16. Each of the terminal pads 27-1, 27-2,..., 27-18 is soldered with wiring from other various electronic devices (not shown) for transmitting / receiving information to / from the multi-channel flexible neural probe. Connected by

  The dimensions of the multi-channel flexible neuroprobe manufactured in this way are as follows. The probe electrode 12 and the electrical wiring 16 portion have a width of about 1.5 mm and a length of about 2.0 cm, for example. 27 has a width of about 1 cm and a length of about 0.5 cm.

  According to the method for manufacturing a multi-channel flexible neuroprobe described above, since a semiconductor substrate can be used and manufactured by a semiconductor manufacturing technique, a probe having a fine structure can be manufactured without requiring complicated manual work.

  The present invention is not limited to the embodiment described above. For example, the entire multi-channel flexible neuroprobe or the dimensions of each part, or the number of probe electrodes and probe conductors are merely examples, and it goes without saying that the multi-channel flexible neuroprobe can be formed in various dimensions or numbers as required.

Further, although polyimide resins 23 and 23 'are used as flexible insulating substrates, other polymer materials may be used. For example, by using a transparent polymer such as a polyparaxylylene-based polymer known under the trade name Parylene ( registered trademark) , when inserting a probe into a living body, while looking at the cells inside the living body, etc. Can be inserted. It is also possible to use polydimethylsiloxane (PDMS) or thick film resist SU-8 (trade name).

Hereinafter, the “polyparaxylylene-based polymer” is referred to as a trade name “Parylene” for the sake of explanation. Since the parylene coating is performed by polymerization of a reactive gas, the thickness of the thin film can be controlled. Furthermore, since it is a gas, the pressure is constant and a uniform thin film can be formed. Parylene is characterized by good biocompatibility, insulation, and flexibility when made into a thin film. The parylene thin film is transparent and excellent in water repellency, gas barrier properties, chemical resistance, and thermal stability. For this reason, it is a material suitable as an insulating film of a nerve electrode.

  FIG. 7 is a cross-sectional view showing an outline of a method for manufacturing a multichannel flexible neuroprobe when parylene is used as an insulating substrate. As shown in FIG. 6A, a photoresist 62, a parylene layer 63, and an aluminum layer 64 are formed by coating on a silicon substrate 61, and the aluminum layer 64 is patterned as shown in FIG. Electrode pads and wiring are formed.

  Here, the parylene layer 63 is formed by vapor deposition using a parylene vapor deposition apparatus. This apparatus includes a vaporization chamber, a thermal decomposition chamber, a vapor deposition chamber, and a vacuum pump, and gas is sent to the vaporization chamber, the thermal decomposition chamber, and the vapor deposition chamber by the vacuum pump. First, diparaxylene produced from paraxylene is vaporized by introducing it into the vaporizing chamber and heating it. This gas is sent to the thermal decomposition chamber and thermally decomposed to produce a highly reactive radical paraxylene monomer. This gas moves to the vapor deposition chamber and is adsorbed and polymerized on the silicon substrate 61, whereby a high molecular weight parylene thin film is formed.

  Next, as shown in FIG. 3C, the entire parylene layer 63 'is coated to form an insulating layer. Next, as shown in FIG. 4D, a copper (Cu) layer 65 is coated on the entire surface and patterned by wet etching to form a mask. Then, as shown in FIG. 5E, the peripheral contour 66 of the probe electrode and the parylene layers 63 and 63 ′ of the recording pad portion 67 are removed by oxygen plasma treatment through this mask. Next, as shown in FIG. 5F, the silicon substrate 61 is peeled from the parylene layer 63 by etching the photoresist 62 with acetone. Further, a metal conductor 68 such as nickel is plated on the recording pad portion 67 from which the parylene layer 63 has been removed. Then, as shown in FIG. 6G, the probe conductor made of the aluminum layer 64 sandwiched between the parylene layers 63 and 63 ′ is bent to form a probe electrode portion.

  In the above-described embodiment, as shown in FIG. 7A, a photoresist 62, a parylene layer 63, and an aluminum layer 64 are formed by coating on a silicon substrate 61. However, silicon does not pass through the photoresist 62. The parylene layer 63 and the aluminum layer 64 may be directly laminated on the substrate 61 by coating. That is, in the above-described embodiment, the photoresist 62 is provided for peeling the silicon substrate 61 from the parylene layer 63, but the parylene layer 63 directly formed on the silicon substrate 61 is utilized by its flexibility. It can be peeled off by mechanical pulling. In this case, a surface active agent such as micro-90 manufactured by International Products Corporation is applied in advance to the surface of the silicon substrate 61, and a parylene layer 63 and an aluminum layer 64 are laminated thereon by coating. In addition, the adhesion between the silicon substrate 61 and the parylene layer 63 is lowered, and peeling becomes very easy. However, when the adhesion between the silicon substrate 61 and the parylene layer 63 is excessively lowered, there arises a problem that the parylene layer 63 is peeled off from the silicon substrate 61 on the parylene layer 63 during the manufacturing process of the electrode pad. Therefore, a thermal oxide film is formed on the surface of the silicon substrate 61, and the parylene layer 63 and the aluminum layer 64 are laminated thereon by coating, thereby preventing the above problem and cracking the laminated body after manufacturing the parylene laminated body. It is possible to peel from the silicon substrate 61 without causing the above.

  In the embodiment described above, aluminum is used as the probe and wiring material, but it is also possible to use conductive polymer or polysilicon instead.

DESCRIPTION OF SYMBOLS 11 Insulation board | substrate 12 Probe electrode 13-15 Probe conductor 13-1, 14-1, 15-1 Recording pad 16 Electrical wiring 21 Si substrate 22 Ni layer 23 1st layer polyimide resin layer 23 '2nd layer polyimide resin layer 24 Metal layer 25 Through hole 26 Flexible insulating substrate 27 Terminal pad

Claims (2)

A probe electrode formed by a plurality of probe conductors sandwiched between a pair of flexible insulating substrates made of a polyparaxylylene-based polymer and standing at a predetermined angle with respect to the surfaces of these insulating substrates, and the probe electrodes The electrical wiring connected to the end of the insulating substrate surface side and sandwiched between a pair of flexible insulating substrates that are also made of polyparaxylylene-based polymer, and the plurality of probe conductors forming the probe electrode are different And a recording pad formed so as to expose a part of each probe conductor by providing a through hole in an insulating substrate that sandwiches the probe conductor at a position. . The probe electrode is in the flexible insulating substrate, a flexible neural probe according to claim 1, wherein the provided plurality of lines.

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