WO2008008755A1 - Bi-planar electrode with shunting gates - Google Patents
Bi-planar electrode with shunting gates Download PDFInfo
- Publication number
- WO2008008755A1 WO2008008755A1 PCT/US2007/073124 US2007073124W WO2008008755A1 WO 2008008755 A1 WO2008008755 A1 WO 2008008755A1 US 2007073124 W US2007073124 W US 2007073124W WO 2008008755 A1 WO2008008755 A1 WO 2008008755A1
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- WO
- WIPO (PCT)
- Prior art keywords
- electrode
- carrier
- neural stimulator
- electrodes
- signal source
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36071—Pain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0526—Head electrodes
- A61N1/0541—Cochlear electrodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0551—Spinal or peripheral nerve electrodes
- A61N1/0553—Paddle shaped electrodes, e.g. for laminotomy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/36036—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the outer, middle or inner ear
- A61N1/36038—Cochlear stimulation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36103—Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36125—Details of circuitry or electric components
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/372—Arrangements in connection with the implantation of stimulators
- A61N1/375—Constructional arrangements, e.g. casings
Definitions
- the present invention relates to electrodes for neural stimulation and, more particularly, to such electrodes disposed on opposite sides of a carrier.
- a cochlear implant is a small electronic device, part of which is placed under the skin, behind the ear, of a profoundly deaf or severely hard of hearing person.
- the cochlear implant receives signals from a microphone and electrically stimulates auditory nerves of the wearer.
- hearing through a CI may be different than normal hearing, the wearer perceives sounds and another person can orally communicate with the wearer.
- CI and other neural stimulation is accomplished by placing at least one electrode near neural tissue and sending an electrical signal to the electrode.
- the electrical signal is produced with reference to a second (ground) electrode. That is, the signal is delivered across the two electrodes.
- the second electrode may be placed near the neural tissue or some distance from the neural tissue.
- the neural tissue is typically stimulated with a bi-phasic pulse, i.e., first a positive pulse is sent to the electrode, followed almost immediately thereafter by a negative pulse. Better results are obtained from better focused electrical stimulation.
- Neural tissues are typically very small. To achieve desired results, selected individual nerves should be stimulated. However, prior art neural stimulation apparatus is unable to deliver well-focused electrical stimulation to neural tissue.
- a conventional longitudinal bipolar neural stimulation scheme includes two conducting electrodes arranged side-by-side on an insulated carrier.
- a signal is fed to a first of the two electrodes, and the other electrode acts as a ground.
- the positive phase of the stimulation signal current flows from one of the electrodes, through the stimulated tissue, into the other (ground) electrode.
- the negative phase of the stimulation signal the current flows in the opposite direction, i.e., out of the ground electrode, through the stimulated tissue, and into the first electrode. Consequently, each of the electrodes acts as a stimulation point, and the stimulation is not well focused.
- a conventional longitudinal tripolar scheme includes two ground electrodes flanking a center electrode. In this case, the amount of current that flows through each of the two flanking electrodes is one-half the amount of current that flows through the center electrode. Tripolar schemes produce reasonably well focused stimulation, however they require three electrodes.
- An embodiment of the present invention provides a neural stimulator that includes a nonconductive carrier.
- the carrier has a first side and a second side substantially opposite the first side.
- At least one first electrode is disposed on the first side of the carrier, and at least one second electrode disposed on the second side of the carrier.
- the at least one first electrode is not electrically connected to the at least one second electrode.
- the carrier may have a circular, oval, rectangular or other cross-sectional shape.
- Each of the at least one first electrode may correspond to one of the at least one second electrode.
- each of the at least one second electrode may be centered on a line that perpendicularly bisects the corresponding first electrode.
- each of the at least one second electrode may be not centered on a line that perpendicularly bisects the corresponding first electrode
- the neural stimulator may also include a signal source connected to one of the at least one first electrode and to the corresponding second electrode.
- the carrier may include at least one shunt gate therethrough.
- each shunt gate defines a low-impedance electrical path through the carrier.
- Some or all of the at least one shunt gate may define a bore through the carrier.
- some or all of the at least one shunt gate may include an electrically conductive material.
- Some or all of the second electrode may include a ring electrode.
- Some or all of the ring electrode may be formed by a photolithographic process.
- some or all of the ring electrode may be formed by a electrodeposition process.
- some or all of the ring electrode may be formed by a laser ablation deposition process.
- the at least one first electrode may include a plurality of electrodes arranged in an array.
- the at least one second electrode may include a plurality of electrodes, each of the plurality of electrodes including a ring electrode.
- the carrier may include at least one shunt gate proximate each first electrode. In this case, each shunt gate defines a low-impedance electrical path through the carrier.
- each of the at least one first electrode includes at least one ear disposed below a surface of the carrier.
- the at least one first electrode includes a plurality of first electrodes in a region of the first side of the carrier. The region includes space between the plurality of first electrodes.
- the at least one second electrode includes an electrically conductive surface on the second side of the carrier. The surface has an area at least as large as the region on the first side of the carrier.
- Fig. 1 is cross-sectional and top view of a neural stimulator, according to the prior art
- Fig. 2 is cross-sectional and top view of another neural stimulator, according to the prior art
- Fig. 3 is cross-sectional and top view of yet another neural stimulator, according to the prior art
- Fig. 4 is cross-sectional and top view of a neural stimulator, according to one embodiment of the present invention.
- Fig. 5 is cross-sectional view of a neural stimulator, according to another embodiment of the present invention
- Fig. 6 is a top view of the neural stimulator of Fig. 5;
- Fig. 7 is a top view of several exemplary shapes and arrangements of shunt gates, according to several embodiments of the present invention.
- Fig. 8 is a top view of a neural stimulator, according to yet another embodiment of the present invention.
- Fig. 9 is a bottom view of the neural stimulator of Fig. 8;
- Fig. 10 is a close-up view of a ring electrode, according to one embodiment of the present invention.
- Fig. 11 is a close-up view of a portion of a neural stimulator, according to one embodiment of the present invention
- Fig. 12 is a close-up top view and two sectional views of electrode ears, according to one embodiment of the present invention
- Fig. 13 is a cross-sectional view of a portion of a neural stimulator, according to one embodiment of the present invention.
- Fig. 14 is a cross-sectional view of a portion of a neural stimulator, according to another embodiment of the present invention.
- one or more pairs of electrodes are disposed on an insulated carrier, such that one of each pair of the electrodes is disposed on one side of the carrier, and the other of the pair of electrodes is disposed on an opposite side of the carrier.
- An electrical stimulation signal is delivered across the pair of electrodes.
- Fig. 1 is a section and top view of a conventional longitudinal bipolar neural stimulator 100.
- the stimulator 100 includes an electrically nonconductive carrier 102 and two electrically conductive electrodes 104 and 106 disposed on the carrier 102.
- the electrodes 104 and 106 are fed, via conductive leads (not shown), by a signal source (not shown).
- a signal source not shown.
- one of the electrodes 104 may be fed with a positive pulse (as indicated by the plus sign), and the other electrode 106 may form a return path (as indicated by the minus sign) for the stimulation signal.
- Arrows 108 and 110 indicate the general direction of current (I) flow. During another phase, the current flows are reversed.
- neural tissue 112 is stimulated from two locations, namely electrodes 104 and 106, and the stimulation is not well focused.
- the amount of current (I) flowing through one of the electrodes 104 into or out of tissue adjacent the electrode 104 is equal to the amount of current (I) flowing through the other electrode 106 out of or into tissue adjacent the other electrode 106. In other words, equal currents flow through the two electrodes 104 and 106.
- Fig. 2 is a section and top view of a conventional longitudinal tripolar neural stimulator 200.
- the stimulator 200 includes three electrodes 202, 204 and 206 on a nonconductive carrier 208. Two of the electrodes 204 and 206 are electrically connected together, such as by a lead 210.
- the current that flows through the center electrode 202 is designated I. One-half of this current (i.e., 1/2) flows through each of the two outer electrodes 204 and 206. Again, the stimulation is not well focused.
- Fig. 3 is a section view of yet another conventional neural stimulator 300.
- the stimulator 300 includes a nonconductive carrier 302 and two electrodes 304 and 306.
- the two electrodes 304 and 306 are electrically connected together, such as by a lead 308. Consequently, half the stimulation current (1/2) flows through each of the two electrodes 304 and 306.
- the stimulation signal is provided with reference to a distant ground electrode (not shown). As with the other prior- art neural stimulators, the stimulation is not well focused.
- Fig. 4 is a section view of a neural stimulator 400, according to one embodiment of the present invention.
- the stimulator 400 includes a nonconductive carrier 402 and two conductive electrodes 404 and 406 disposed on opposite sides of the carrier 402.
- the two electrodes 404 and 406 are not electrically connected together.
- the stimulating signal is provided (via leads, not shown) to one of the electrodes 404 with respect to the other electrode 406. That is, the signal is provided across the electrodes 404 and 406.
- the same amount of current (I) flows through each of the electrodes 404 and 406.
- Arrows 408 and 410 indicate current flow during a portion of the stimulation signal. During another portion of the stimulation signal the current flow may be reversed.
- the carrier 402 can be round or oval in cross-sectional shape.
- the carrier 402 can be rectangular in cross- sectional shape. In other embodiments (not shown), the carrier 402 can have other cross-sectional shapes.
- the thickness 412 of the carrier 402, i.e., the distance between the two electrodes 404 and 406, along with the cross-sectional shape of the carrier 402 can be selected to provide a stimulation field having desired characteristics. For example, a larger distance between the electrodes 404 and 406 requires a less powerful stimulation signal than a smaller separation distance; however, a larger separation often yields a less focused stimulation field.
- the neural tissue 112 is stimulated from a single point, i.e., the electrode 404 facing the neural tissue 112.
- the stimulator 400 is positioned such that it is in a plane parallel to a plane of the neural tissue 112.
- the stimulating electrode 404 is in the parallel plane.
- the other electrode 406 is also in a plane parallel to the neural tissue 112, but the other electrode's 406 plane is located on the opposite side of the stimulating electrode 404.
- the plane of the other electrode 406 is referred to herein as "antineural," i.e., on the opposite side from the plane of the stimulating electrode 404. I have discovered that disposing the return electrode 406 antineural focuses the stimulating signal.
- the neural stimulator 400 can have any shape, such as round or rectangular.
- the electrodes 404 and 406 and leads can be fabricated using conventional photolithographic, electrodeposition, pulsed laser ablation deposition or other techniques. For example, platinum can be deposited on a conventional carrier.
- shunt gates 500 are included in the carrier 402 of the neural stimulator 400.
- Fig. 6 is a top view of the neural stimulator 400.
- the shunt gates 500 provide conductive or low-impedance paths through the carrier 402 for at least some of the stimulation signal.
- the shunt gates 500 provide improved focus of the stimulation signal.
- the shunt gates 500 can be open passages, holes, grooves, slots or other openings (collectively herein referred to as "bores") formed through or on the carrier 402. In this case, conductive body fluid or tissue fills the shunt gates 500.
- the carrier 402 can be made with shunt gates 500 formed of an electrically conductive or low impedance (collectively herein referred to as "low-impedance") material, such as electrodeposited platinum columns or a conductive polymer, such as polypyrrole.
- some of the shunt gates 500 are open passages and others are low impedance material in the carrier 402.
- a low resistance (R) can be achieved by using a large area (A) and/or a small length (L).
- Fig. 7 illustrates other exemplary, but non-limiting, shapes, symmetries/asymmetries and arrangements.
- shunt gates need not be perpendicular to the surface of the carrier.
- a shunt gate 502 can be formed at an angle other than 90° to the surface of the carrier 402.
- the distances between the shunt gates 500 and the stimulating electrode 404 can be varied. That is, not all the shunt gate 500 need be disposed the same distance from the stimulating electrode 404.
- the number, shape(s), arrangement, angle(s) and placement(s) (relative to the stimulating electrode 402) of the shunt gates 500 can be selected to shape and orient the stimulation field, as desired.
- the distance between the stimulating electrode 404 and the shunt gates 500 can be selected to generate a stimulation field having a desired shape and/or orientation.
- the shunt gates 500 can be positioned symmetrically or asymmetrically around the stimulating electrode 404.
- the thickness 412 of the carrier can be selected to achieve a desired path length between the stimulating electrode 412 and the return electrode 406. As long as the path length is relatively low, the stimulation field may be affected by the other geometric parameters described above.
- the above-described neural stimulator 400 includes one stimulating electrode 404 and one return electrode 406.
- a neural stimulator 800 shown in Fig. 8 several stimulating electrodes 802 are disposed on a single nonconductive carrier 804.
- the neural stimulator 800 may contain hundreds of stimulating electrodes 802 on a carrier that may be about 1 cm by 3 cm. Other numbers of stimulating electrodes 802 and other dimensions may be used.
- each of the electrodes 802 is connected by a separate lead (not shown) to a signal source (not shown).
- each electrode 802 has its own signal source.
- a switching matrix or other circuit (not shown) is connected between one or more signal sources and the electrodes 802 to select which electrode(s) 802 is provided with a stimulating signal at a given time and, optionally, which signal source is connected to the electrode(s) 802.
- each of the electrodes 802 can be separately supplied with a stimulation signal, or not supplied with any signal. Consequently, as may be the case in a CI, individual areas of neural tissue can be stimulated by individual electrodes 802 or groups of electrodes 802.
- groups of the electrodes 802 can be electrically connected together and, thus, receive a common stimulation signal.
- each of the stimulating electrodes 802 has a corresponding return electrode (not visible in Fig. 8) disposed on the opposite side of the carrier 804.
- These return electrodes can each have an associated lead in the carrier 804 to provide a return path to the signal source.
- the return electrodes can, but need not, have the same size and shape as the corresponding stimulating electrodes 802. Alternatively, the return electrodes can be larger or smaller than the corresponding stimulating electrodes 802. Similarly, the return electrodes can have different shapes than the stimulating electrodes 802.
- each return electrode is centered on a line that extends perpendicularly through the center of the corresponding stimulating electrode 802. In other embodiments, the return electrodes are not co-centered with their corresponding stimulating electrodes 802.
- a switching matrix or other circuit is used to change, from time to time, which return electrode corresponds to a given stimulating electrode 802.
- each return electrode is a conductive ring 900, as shown in Fig. 9.
- Fig. 9 is a bottom view of the neural stimulator 800 of Fig. 8.
- the return electrodes 900 can be made in other solid or open shapes, such as polygons. Open-shape polygonal return electrodes are referred to herein as "rings," regardless of their shape.
- Each return electrode 900 is preferably centered on its corresponding stimulating electrode
- the return electrodes need not be centered on their corresponding stimulating electrodes.
- a switching matrix or other circuit is used to change, from time to time, which return electrode 900 corresponds to a given stimulating electrode.
- each ring 900 that is exposed to tissue is approximately equal to the total conducting surface area of the corresponding stimulating electrode 802 that is exposed to tissue.
- the return electrodes 900 may be fabricated on the carrier 804 using photolithographic, electrodeposition, pulsed laser ablation deposition or other techniques.
- a single ring electrode 900 of which is shown in Fig. 10 each stimulating electrode 802 is about 300 ⁇ in diameter, and each ring electrode 900 has an inside diameter 1000 of about 600 ⁇ . (In Fig.
- each ring electrode 900 can be calculated, based on the diameter of the stimulating electrode 802 and the diameter 1000 of the ring 900, such that the two electrodes have approximately equal surface areas, as discussed above.
- the width 1002 of the ring electrode 802 is significantly less than the diameter of the stimulating electrode 802.
- the diameters of the ring 900 and the stimulating electrode 802 may be related as follows:
- D out is the outside diameter of the ring 900
- D 1n is the inside diameter 1000 of the ring 900
- D is the diameter of the stimulating electrode 802.
- stimulating electrodes 802 and/or other sizes of ring electrodes 900 can be used.
- stimulating electrodes smaller than about 300 ⁇ in diameter may be used, and ring electrodes 900 having inside diameters 1000 of about 1 or 2 mm can be used.
- groups of the return electrodes 900 can be electrically connected together to provide a common ground return electrode for a group of the stimulating electrodes 802.
- a single conductive plane is used instead of individual return electrodes 900.
- a carrier 1100 includes shunt gates 1102 between the ring electrodes 900 and the stimulating electrodes 802.
- the carrier 1100 includes shunt gates 1104 outside the ring electrodes 900.
- the shunt gates 1102 and 1104 can be any shape or size and have any orientation, relative to the stimulating electrodes 802 and the ring electrodes 900.
- some or all the ring electrodes 900 can be electrically connected together.
- the bottom of the carrier 1100 is largely covered by a single conductive return electrode, perforated by the shunt gates 1102 and/or 1104.
- Electrode Anchors As noted, the electrodes are made of conductive material held in a non-conductive carrier.
- a carrier 1200 includes an electrode 1202.
- the surface 1204 of the electrode 1202 is co- planar with the surface 1206 of the carrier 1200, although the surface 1204 of the electrode 1202 can be proud of, or depressed below, the surface 1206 of the carrier 1200.
- Anchors (ears) 1208 are formed on the electrode 1202 and beneath the surface 1206 of the carrier 1200 to secure the electrode 1202 to the carrier 1200.
- a lead 1210 connected to the electrode 1202 also secures the electrode 1202 to the carrier 1200.
- Similar anchors (ears) can be formed on ring (or other shape) electrodes (not shown) to secure the ring electrodes to the carrier 1200.
- a carrier 1300 can include four electrodes 1, 2, 3 and 4, any pair of which can be connected to a signal source (not shown).
- Each of the electrodes 1, 2, 3 and 4 has a lead (not shown), via which the electrode can be connected to the signal source, such as through a switching matrix or other circuit (not shown).
- Table 1 lists the possible combinations of electrodes that can be connected to the signal source.
- a return electrode that is not directly behind a stimulating electrode creates a stimulation field that is directed "off-axis," i.e., not along an axis that perpendicularly bisects the stimulating electrode.
- a carrier that includes more than two return electrodes in the antineural plane, as shown in Fig. 14, and pairing a particular stimulating electrode, such as electrode 2, with one or more of the return electrodes 3-7 the stimulation field can be steered toward selected portions of the neural tissue 112. This steering can provide more spatial resolution than simply selecting a different pair of electrodes that are positioned directly opposite each other on the carrier.
- the return electrodes 3-7 need not be positioned directly opposite the stimulating electrodes, and the carrier can have more or fewer return electrodes than stimulating electrodes.
- Figs. 13 and 14 include a small number of electrodes, these drawings can alternatively be interpreted to represent only a portion of a neural stimulator that includes many more electrodes (not shown).
- the above-described shunt gates can be combined with angled bipolar stimulation. Other combinations of the features described herein are also possible.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009519626A JP4608010B2 (en) | 2006-07-14 | 2007-07-10 | Biplanar electrode with short-circuit gate |
EP07812748A EP2040793B1 (en) | 2006-07-14 | 2007-07-10 | Bi-planar electrode with shunting gates |
AT07812748T ATE481128T1 (en) | 2006-07-14 | 2007-07-10 | BIPLANAR ELECTRODE WITH BLOCKING GATES |
CA2657840A CA2657840C (en) | 2006-07-14 | 2007-07-10 | Bi-planar electrode with shunting gates |
DE602007009238T DE602007009238D1 (en) | 2006-07-14 | 2007-07-10 | BIPLANIC ELECTRODE WITH BARRIER-GATES |
CN2007800322874A CN101511424B (en) | 2006-07-14 | 2007-07-10 | Bi-planar electrode with shunting gates |
AU2007272561A AU2007272561B2 (en) | 2006-07-14 | 2007-07-10 | Bi-planar electrode with shunting gates |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/487,162 | 2006-07-14 | ||
US11/487,162 US7706888B2 (en) | 2006-07-14 | 2006-07-14 | Bi-planar electrode with shunting gates |
Publications (1)
Publication Number | Publication Date |
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WO2008008755A1 true WO2008008755A1 (en) | 2008-01-17 |
Family
ID=38610930
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/073124 WO2008008755A1 (en) | 2006-07-14 | 2007-07-10 | Bi-planar electrode with shunting gates |
Country Status (12)
Country | Link |
---|---|
US (1) | US7706888B2 (en) |
EP (1) | EP2040793B1 (en) |
JP (1) | JP4608010B2 (en) |
KR (1) | KR101025645B1 (en) |
CN (1) | CN101511424B (en) |
AR (1) | AR062060A1 (en) |
AT (1) | ATE481128T1 (en) |
AU (1) | AU2007272561B2 (en) |
CA (1) | CA2657840C (en) |
DE (1) | DE602007009238D1 (en) |
RU (1) | RU2465930C2 (en) |
WO (1) | WO2008008755A1 (en) |
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RU2465930C2 (en) | 2012-11-10 |
DE602007009238D1 (en) | 2010-10-28 |
AR062060A1 (en) | 2008-10-15 |
CA2657840C (en) | 2011-11-22 |
EP2040793B1 (en) | 2010-09-15 |
CN101511424B (en) | 2012-04-25 |
RU2009105195A (en) | 2010-08-27 |
CN101511424A (en) | 2009-08-19 |
KR20090039747A (en) | 2009-04-22 |
KR101025645B1 (en) | 2011-03-30 |
ATE481128T1 (en) | 2010-10-15 |
CA2657840A1 (en) | 2008-01-17 |
AU2007272561A1 (en) | 2008-01-17 |
JP2009543605A (en) | 2009-12-10 |
EP2040793A1 (en) | 2009-04-01 |
AU2007272561B2 (en) | 2010-07-22 |
US7706888B2 (en) | 2010-04-27 |
AU2007272561A2 (en) | 2009-03-12 |
US20080015669A1 (en) | 2008-01-17 |
JP4608010B2 (en) | 2011-01-05 |
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