This application claims priority to and the benefit of Japan Patent Application No. 2011-215939, filed on Sep. 30, 2011, in the Japan Patent Office, each of the disclosure, claims, abstract, and drawings of which is incorporated herein by reference in its entirety.
1. Technical Field
The present disclosure relates to a stimulus electrode to deliver electrical stimulation to a region of a biological tissue and a method of producing the stimulus electrode.
2. Foundation
An electrical stimulation device for a living body that applies electrical stimulation to a region of a biological tissue so as to regulate a bodily function is being studied. Two typical examples of devices for a living body that deliver electrical stimulation are a cochlear implant and a cardiac pacemaker. The cochlear implant stimulates the auditory nerve of a patient so as to transmit sound vibration to auditory ossicles. The cardiac pacemaker is implanted in a patient's chest, and electrically stimulates a heart muscle, thus controlling an irregular heartbeat. Another typical electrical stimulation device for a living body is a vision restoration assist apparatus (as disclosed in JP-A-2009-082496). The vision restoration assist apparatus outputs an electrical stimulation pulse signal (electric charge) via an electrode, and electrically stimulates a cell forming a retina, thus promoting vision restoration.
The electrical stimulation device delivers a predetermined amount of electric charge via the electrode so as to sufficiently stimulate the cell. The stimulus electrode is arranged in a compact space in vivo. In view of this, it is preferred that the electrode have a minimized size to reduce the patient's discomfort. The ability of the stimulus electrode to deliver denser electric charges becomes higher in proportion to a surface area of the electrode.
Especially, the electrical stimulation device with a plurality of electrodes needs to have a reduced size of the electrode and an expanded surface area. Therefore, this application is directed toward increasing the surface area of the electrode by generating a redox reaction to make its surface rough by etching (as disclosed in JP-A-2011-030734).
This type of application ensures the increased surface area of the electrode. However, this method has the following problems: 1. This limits the kinds of electrode material that can be surface treated with this method. 2. The reproducibility of the surface conditioning pattern of the electrode may be difficult. The present disclosure provides a stimulus electrode for biological a tissue that is more stable in property and a method of producing the stimulus electrode.
According to a first aspect of the present disclosure, there is provided a method of producing a stimulus electrode for a biological tissue. The method includes irradiating a surface of an electrode with an ultrashort pulse laser to form a plurality of deformations. According to a second aspect of the present disclosure, there is provided a stimulus electrode for a biological tissue. The stimulus electrode includes a surface on which a plurality of deformations is formed by an irradiation of an ultrashort pulse laser.
Preferred embodiments of the present invention will be described below with reference to the accompanying drawings, in which like reference characters designate similar or identical parts throughout the several views thereof.
The electrode 1 has a predetermined three-dimensional shape. The electrode 1 has a distal end (an upper end) 1a that has a curved surface with a predetermined curvature (a curvature radius). The distal end 1a of the electrode 1 includes a plurality of holes 1c. In contrast, the electrode 1 has a side face 1b without the holes 1c. Thus, the side face 1b is smoother than a surface at the distal end 1a.
While the holes 1c are not formed all over the surface of the electrode 1, the holes 1c are formed only on the surface of the electrode 1 at the distal end 1a. This increases only density of the electric charges that can be discharged from a local region at the distal end 1a. This configuration enables appropriate electrical stimulation to the local region of a biological tissue.
Next, a method of producing the electrode 1 will be described.
Here, the three-dimensional electrode 1 is formed to have a bullet shape that has an outer diameter of 100 to 500 μm and a height of 100 to 500 μm. The electrode 1 employs a well-known metal with biocompatibility as a forming material. Here, a platinum (Pt) material is chosen. The electrode 1 may be formed of other materials such as gold, titanium nitride, pure iridium, iridium oxide, tantalum, and a mixture of these materials. In some embodiments, the electrode 1 is an alloy.
The electrode 1 may be formed in various sizes and shapes according to its usage using well-known metal processing. For example, the metal processing includes a cutting work, machining, lathing, filing and the like. This forms, for example, a plate-shaped electrode with a predetermined thickness. In some embodiments, the electrode has a solid volume space less than 10 mm3. In some embodiments, the solid volume space is less than 1 mm3. Next, a surface treatment is performed on the electrode 1 so as to increase a surface area (charge injection capability) of the electrode 1. In this embodiment, the surface of the electrode 1 is irradiated with an ultrashort pulse laser to form the plurality of holes 1c on the surface of the electrode 1, thus increasing the surface area (charge injection capability). The ultrashort pulse laser is a laser with a pulse width from nanosecond to femtosecond. In some embodiments, the pulse width is measured at the full-width half-maximum. In some embodiments, the pulse width ranges from 1 fs to 999 ps. In some embodiments, the pulse width ranges from 20 fs to 900 fs or from 100 fs to 700 fs. In some embodiments, the ultrashort pulse has a pulse energy ranging from 0.01 μJ to 10 mJ. In some embodiments, the pulse energy ranges from 0.1 μJ to 5 mJ or from 0.9 μJ to 2 mJ. In some embodiments, the ultrashort laser has pulse repetition frequency ranging from 100 Hz to 100 Mhz. In some embodiments, the pulse repetition frequency ranges from 100 kHz to 80 MHz or from 200 kHz to 20 MHz. In some embodiments, the pulse repetition frequency ranges from 500 Hz to 5 kHz or from 1 kHz to 4 kHz. Such features are available from mode locked lasers such as solid state (Ti:sapphire and the like) or dye mode locked lasers. In some embodiments, the laser pulse has a maximum intensity wavelength ranging from 700 nm to 1,200 nm or from 780 nm to 1,100 nm. In some embodiments, e.g., the maximum of the bandwidth of the laser pulse is 780 to 800 nm or 1020 to 1060 nm.
The ultrashort pulse laser with a short pulse width is used for the surface treatment on the electrode 1. This forms more holes 1c on the surface of the electrode 1. This also restricts heat, which is generated by laser irradiation, from propagating near the holes 1c, thus accurately forming the holes 1c. Using a series of ultrashort laser pulses having one or more features above makes it possible to avoid the reflow material, i.e., roughness induced by the creation of high temperatures within or adjacent to the region near the holes 1c.
An exemplary laser irradiation device will be described.
The laser light source 110 employs a device that emits an ultrashort pulse laser with a pulse width from nanosecond to femtosecond. The ultrashort pulse laser generates plasma (causing breakdown) at the focal point of the laser (a laser absorption point). Emitting the laser cuts an object (a part of the electrode) at the focal point or waist of the pulse laser.
The irradiation optical system 120 includes a scanning unit (an optical scanner) 121, a focus shifting unit (a focus shifter) 122, and an objective lens 124. The scanning unit 121 two-dimensionally (in the XY direction) scans (deflects) the laser absorption point (a focus position) of the pulse laser on a target surface. The focus shifting unit 122 shifts the laser absorption point of the pulse laser in the optical axis direction (the Z direction). The objective lens 124 focuses the laser and forms an image on the target surface. The scanning unit 121 and the focus shifting unit 122 constitute a moving optical system that three-dimensionally moves the absorption point of the laser light toward the electrode 1.
The controller 150 controls operations of the whole laser irradiation device 100. The controller 150 is coupled to an input unit 151, a foot switch 152, a memory 153, and the like. The input unit 151 is used for setting a laser irradiation condition and a laser scanning condition. The foot switch 152 is used to input a trigger signal to begin laser irradiation. The memory 153 preliminarily stores various conditions.
The laser light source 110 irradiates the surface of the electrode 1 with a laser beam from above, thus causing breakdown at a laser absorption point of the laser. This causes mechanical destruction (for example, cracking) having a size of the absorption point on the surface of the electrode 1. As illustrated in
After forming the hole 1c in a predetermined position on the surface of the electrode 1, the scanning unit 121 and the focus shifting unit 122 are driven so as to move the laser irradiation position in a horizontal direction (the XY direction). Thus, another hole 1c is formed in a different position at the distal end 1a. Thus, three-dimensionally moving the laser absorption point allows the formation of a plurality of holes 1c at desired positions at the distal end 1a of the electrode 1 by laser irradiation.
In this embodiment, the controller 150 drives the moving optical system to adjust the laser irradiation position on the surface of the electrode 1, thus forming the plurality of holes 1c in different positions at the distal end 1a of the electrode 1. Another configuration is available for moving the laser irradiation position on the surface of the electrode 1. The configuration fixes the laser irradiation device 100 and moves the electrode 1 in a three dimensional direction. For example, the electrode 1 may be placed on a stage (not shown). Then, the controller 150 moves the stage in a three dimensional direction. As another configuration, the respective drive controls of the moving optical system 122 and the stage may be combined together. That is, any other configuration is available insofar as the laser irradiation position is adjusted relative to the electrode 1.
The hole 1c has a diameter, a depth, a positional relationship (the distance) with the adjacent hole 1c, which are determined with a irradiation condition. The irradiation condition may be preliminarily stored in the memory 153, and selected through the input unit 151. Alternatively, in the case where a condition to form the hole 1c is set through the input unit 151, the controller 150 may automatically determine another condition. For example, the controller 150 automatically sets a position where the adjacent holes 1c are formed depending on the set size of the holes 1c.
Further, in some embodiments, the laser irradiation position in the optical axis direction (the Z direction) be adjusted corresponding to the shape of the electrode 1. Inputting height information and the like of the electrode 1 to the memory 153 allows the controller 150 to recognize the shape of the electrode 1. For example, the height information of the electrode 1 is provided by obtaining variations (Z1−Z0=ΔZ) among heights of other positions (coordinate) (X1, Y1) at the distal end 1a relative to a height (Z0) of the center position (coordinate) (X0, Y0) at the distal end 1a of the electrode 1.
For example, as illustrated in
A method that increases the surface area of the electrode using a conventional technique of a chemical reaction (etching) may cause variation in the surface condition of the electrode due to different kinds of electrode materials. The variation in the surface condition of the electrode 1 occurs even among electrodes with the same electrode material depending on their individual differences after the surface treatment.
In contrast, the present disclosure increases the surface area by irradiating the surface of the electrode 1 with the laser. Thus, the present disclosure sets a laser irradiation condition regardless of the kind of metallic material forming the electrode 1, thus ensuring an electrode with a constant surface condition. That is, the surface treatment using the ultrashort pulse laser ensures the electrodes 1 with the same surface condition regardless of individual differences of the electrodes 1 with high reproducibility.
In this embodiment, platinum is used as an electrode material. In some embodiments, the hole 1c in the electrode 1 has a diameter ranging from 5 μm to 30 μm, In some embodiments, the hole 1c in the electrode 1 has a diameter ranging from 5 μm to 100 μm, and a depth with an aspect ratio equal to or more than 1. The aspect ratio A is a value obtained as a ratio of a depth “a” of the hole 1c to the diameter “d” of the hole 1c, which is expressed by A=d/a. In some embodiments, the aspect ratio ranges from 0.02 to 2 or from 0.04 to 1.5. In some embodiments, the aspect ratio is the average value of the aspect ratio for the set of holes on the electrode.
A diameter smaller than 5 μm of the hole 1c makes it difficult to form the hole 1c on the surface of the electrode 1. This increases the possibility of variation (occurrence of local bias in an amount of increase in surface area) in the surface condition of the electrode 1. On the other hand, a diameter larger than 30 μm of the hole 1c reduces the number of the holes 1c to be formed on the electrode surface, thus tending to restrict the surface area of the electrode 1 from increasing.
The aspect ratio A smaller than 1 makes the depth of the hole 1c shallower, thus restricting the surface area of the electrode 1 from increasing. A larger aspect ratio makes the surface area of the electrode 1 increase more. However, this increases a delay time between an output electric charge from the surface (the upper portion 1b) of the electrode 1 and an output electric charge from inside the hole 1c. Preventing a large delay time is, in some embodiments, used so as not to reduce accuracy of the electric charge (an electrical pulse signal), which is output from the electrode 1. The diameter and the depth, which are described above, of the hole 1c are selected such that the diameter and the depth satisfy these characteristics. The diameter and the depth are combined with the shape and the material of the electrode as needed.
As described above, forming the plurality of holes 1c at the distal end 1a of the electrode 1 by laser irradiation increases the surface area of the electrode 1 (the distal end 1a), thus improving charge injection capability. This ensures the electrodes 1 with the same surface condition regardless of the kind of the electrode material or individual differences of the electrodes with high reproducibility. The holes 1c are formed in a region with the distal end 1a of the electrode 1 at the center. This concentrates injection charges on the distal end 1a of the electrode 1, thus applying accurate (pinpoint) electrical stimulation to the local region of the biological tissue. In contrast, no holes 1c is formed on the side face 1b of the electrode 1 without the laser irradiation. This increases the surface area of the electrode 1 at the distal end 1a without changing the outline shape of the side face of the electrode 1.
In
The diameters of the holes 1c may be formed to vary from the center of the distal end 1a to the periphery. For example, as illustrated in
Furthermore, as illustrated in
In addition, controlling machining (laser processing) corresponding to a shape, usage, and the like of the electrode 1 forms recesses with various shapes on the surface of the electrode 1 using the holes or the grooves. This arbitrarily increases the surface area of the electrode 1, thus arbitrarily increasing charge injection capability of the electrode 1. A known processing to improve charge injection capability may be further performed after the above surface treatment forms the holes 1c on the surface of the electrode 1. For example, processes such as platinum black plating or forming an iridium oxide film may be performed.
Next, an exemplary electrical stimulation device including the electrode 1 where the above surface treatment has been performed will be described. Here, an exemplary vision restoration assist apparatus, which applies electrical stimulation to a patient's retina, will be described.
As illustrated in
Next, the electrode 1 is inserted into a well-known washer 46 from the base of the electrode 1 until the washer 46 is brought into contact with the wires 41. Then, the base is pressed so as to sandwich (couple) the wires 41 between the electrode 1 and the washer 46. The processing is individually performed for the respective electrodes 1, thus electrically coupling the wires 41 to the respective electrodes 1.
Next, as illustrated in
The substrate 43 is formed of resin after the electrodes 1 are arranged in the holes 71 of the above tool 70. For example, as illustrated in
At this time, in this embodiment, the surface treatment by laser on the side face lb of the electrode 1 is not performed, thus preserving the outline shape of the electrode 1. Consequently, gaps are not formed between the electrode 1 and the hole 71, thus preventing the resin from flowing into between the electrode 1 and the hole 71. In view of this, an operation (process) for removing resin adhered to the electrode 1 is omitted. Accordingly, the substrate 43 is more efficiently produced.
In the above description, the substrate 43 includes the electrode 1 on which the surface treatment has preliminarily been performed. In addition, the surface treatment may be performed on the electrode 1 by laser irradiation after the electrode 1 is implanted in the substrate 43. This increases the surface area (charge injection capability) of the electrode 1 (the distal end 1a). This process arranges the respective electrode 1 in a predetermined position on the substrate 43 such that the distal end 1a where the plurality of holes 1c is formed projects from the surface of the substrate 43.
Next, a configuration of the vision restoration assist apparatus will be described.
The implantable device 200b includes a receiving unit 23, which receives a signal from the external device 200a, a controller 25, an electronic circuit 40, and the electrodes 1, which are embedded in the substrate 43. The controller 25 generates an electrical stimulation pulse to be delivered to the respective electrodes 1 based on data for the electrical stimulation pulse, which is received by the receiving unit 23. The controller 25 controls operation of the whole implantable device 200b. The electronic circuit 40 delivers the electrical stimulation pulse to the respective electrodes 1 based on a signal from the controller 25. The electronic circuit 40 is electrically coupled to the respective electrodes 1 via the wire 41.
Photograph data (image data) of an object, which is photographed by the photographing device 12, is transmitted to the converting unit 13a for the pulse signal. The converting unit 13a for the pulse signal converts the photograph data of the object to data for the electrical stimulation pulse. Then, the converting unit 13a for the pulse signal superimposes the data for the electrical stimulation pulse on a carrier wave supplied from the power source 13b, thus transmitting an electromagnetic wave to the implantable device 200b through the transmitting unit 14.
The implantable device 200b receives the signal transmitted from the external device 200a at the receiving unit 23, and transmits the signal to the controller 25. The controller 25 generates electrical stimulation pulses, which are delivered to the respective electrodes 1, and various control signals based on the data for the electrical stimulation pulse, which is received by the receiving unit 23, and transmits the generated signals and pulses to the electronic circuit 40.
The electronic circuit 40 outputs an electrical stimulation pulse from each electrode 1 based on a received signal. The electrical stimulation pulse output from each electrode 1 stimulates a cell forming a retina E (see
The electrode 1 on which the aforementioned surface treatment is performed by laser irradiation is a typical electrical stimulation device for biological tissues. For example, the electrode 1 is used in an electrical stimulation device such as a pacemaker and a cochlear implant. This improves charge injection capability without increasing the size of the electrode 1. The improved charge injection capability of the electrode 1 has an advantage in decreasing the size of the electrode 1. The downsized electrode 1 reduces the discomfort of the patient in which the electrode 1 is to be implanted. This also allows arranging more electrodes 1 in a limited area of biological tissues, thus improving accuracy of the electrical stimulation to the biological tissues.
In the above description, the irradiation of the ultrashort pulse laser generates the mechanical destruction. The mechanical destruction forms the deformation (recess or groove) on the electrode 1, thus increasing the surface area. In addition, irradiating the surface of the electrode 1 with the femtosecond laser may form the recess (groove) with a periodic structure, thus increasing the surface area. The periodic structure is formed such that incident light and reflected light of the laser mutually interfere in the case where an object (electrode) is irradiated with an intense femtosecond laser that is close to a threshold value of the processing. Although the pulse energies noted above are useable, in some embodiments, the pulse energy ranges from 0.5 to 5.0 μJ or from 1.0 to 2.5 μJ. The periodic structure is constituted of a plurality of grooves. The groove has a space frequency and a depth at the same level as a wavelength of the laser, thus increasing the surface area of the electrode. For example, platinum allows many periodic structures with both a pitch (distance) and a depth of several hundred nm to be formed on the surface (electrode surface) corresponding to a laser wavelength. The pitch and the depth of the periodic structure are at the same level as the laser wavelength. In some embodiments, the laser wavelength is altered by frequency up-conversion or down-conversion, using, e.g., a nonlinear optical crystal.
The pitch and the depth of the periodic structure, which are determined by the laser wavelength, equal to or more than 1 nm increases the surface area of the electrode. In some embodiments, pitch and depth of the periodic structure are formed from 200 nm to 1200 nm. This appropriately increases the surface area of the electrode (metal). The periodic structure formed by laser irradiation is formed regardless of the shape of the electrode. Especially, the periodic structure appropriately ensures an increased surface area of the thin electrode 1 where forming the hole or the groove by mechanical destruction is difficult. With another electrode shape (for example, a bullet shape), densely forming the periodic structure in a region that is desired to have high charge density appropriately ensures improved charge injection capability. Furthermore, combination of: a surface treatment where a plurality of holes or grooves are formed by mechanical destruction; and a surface treatment where the periodic structure is formed by femtosecond laser irradiation may be used to increase the surface area (charge injection capability) of the electrode 1.
Next, experimental results where the ultrashort pulse laser is actually used for the surface treatment of the electrode 1 will be described.
A bullet-shaped electrode that was formed of platinum (Pt) as a material and had a diameter of about 500 μm and a height of about 300 μm was used as an electrode. The laser irradiation device (LWL-3030-T10) that was used was made by SIGMA KOKI CO., LTD. The laser irradiation condition included an oscillation frequency of 200 KHz, an average output equal to or more than 400 mW, a pulse width equal to or less than 500 fs, and a pulse repetition frequency of 200 kHz. The laser beam was collected by an objective lens with magnification of 20 times. The electrode is irradiated with a femtosecond laser with a beam diameter of 15 μm at its top surface. The electrode surface condition was observed through Scanning Electron Microscope (SEM). The laser irradiation position (a distance and a location of a hole) with respect to the surface of the electrode was set using CAD.
A platinum foil (plate electrode) with a thickness of 20 μm was used as an electrode. The laser irradiation device that was used was the same as that in Example 1. The irradiation condition of the femtosecond laser included an average output of 1.2 μJ/pulse, a processing speed of 2 mm/s, a spiral pitch of 10 μm, and with trepanning. The laser beam was collected by an objective lens with magnification of 5 times. The same SEM as that in Example 1 was used for the observation of the electrode surface.
The foregoing detailed description has been presented for the purposes of illustration and description. Many modifications and variations are possible in light of the above teaching. It is not intended to be exhaustive or to limit the subject matter described herein to the precise form disclosed. Although the subject matter has been described in language specific to structural features and/or methodological acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims appended hereto.
Number | Date | Country | Kind |
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2011-215939 | Sep 2011 | JP | national |