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
  • A61N1/36128—Control systems
  • A61N1/36146—Control systems specified by the stimulation parameters
  • A61N1/36182—Direction of the electrical field, e.g. with sleeve around stimulating electrode
  • A61N1/36185—Selection of the electrode configuration
• • 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
• • 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
  • A61N1/0529—Electrodes for brain stimulation
  • A61N1/0534—Electrodes for deep brain stimulation
• • 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

Definitions

• FIG. IA shows a prior- art pacer lead configuration using a single conductor in a lead 13.
• the "can" 12 contains drive or sensing electronics that are external to electrode locations 14.
• the can 12 and lead 13 (with its electrode locations 14) is implanted within tissue 17 of an animal, below surface 11 such as a dermal surface.
• An impedance model for the tissues 17 assumes localized impedances 18 physically nearby to the electrode areas 14, and more generalized impedance 19, together defining a return path to the can 12.
• Fig. IB shows a prior-art pacer lead configuration using two conductors 15, 16 in a lead 13. Electrodes at the electrode areas 14 may be selectively communicatively coupled with conductors 15, 16. Drive voltages from the can 12 pass through the conductors 15, 16 to particular electrodes in area 14. The drive voltage will stimulate a region 20 of the tissue 17.
• the selective coupling of electrodes to lead conductors may be achieved for example by means of circuitry and techniques set forth in a multiplex system (e.g., as described in United States Patent publication no. US 20040254483 entitled “Methods and systems for measuring cardiac parameters”; US patent publication number US 20040220637 entitled “Method and apparatus for enhancing cardiac pacing”; US patent publication number US 20040215049 entitled “Method and system for remote hemodynamic monitoring”; US patent publication number US 20040193021 entitled “Method and system for monitoring and treating hemodynamic parameters; and provisional application number
• the region of tissue being stimulated or sensed be on the order of a few hundred microns. If only ways could be found to stimulate and sense such very small regions, it might be possible to sense phenomena on the cellular level, perhaps as specific as the firing of an individual neuron. It might be possible to stimulate similarly small regions. Electrical stimulation might permit treatment, for example, of movement disorders such as Parkinson's and dystonia.
• insertion of a lead for the purposes discussed here be done once and not more than once.
• Each insertion can cause trauma to tissue. If a lead were inserted, and later needed to be removed so that a different lead could be inserted (for example with a goal of slightly different electrode positioning) this would cause otherwise unneeded trauma to the nearby tissue. If on the other hand, a lead could be provided that permits great flexibility of use later, this would reduce how often a lead removal and replacement would be called for.
• Spatial arrays of electrodes are provided, each array in a region of tissue.
• the electrodes of an array are connected so that some of the electrodes serve as shield electrodes relative to a pair of electrodes used for pulse stimulation or sensing of electrical activity, or both.
• the shield electrodes are connected together, defining an electrical node, the node defining a stable potential in predetermined relationship with power supply levels or with reference voltages for sensing circuitry. Multiplexing techniques may be employed so that sensed activity at each of several electrode locations can be communicated to electronics external to the electrode locations.
• Fig. IA shows a prior- art pacer lead configuration using a single conductor in a lead
• Fig. IB shows a prior- art pacer lead configuration using two conductors in a lead
• Figs 2A, 2B, 2C, 2D, and 2E show models for stimulation fields when various combinations of electrode selection and drive are employed;
• Fig. 3 shows an exemplary crosspoint matrix (switching fabric) that may be used in an integrated circuit chip according to an embodiment of the invention
• Fig. 4 shows an exemplary selection of electrodes serving as shield electrodes tied to a common node and other electrodes providing sensing or stimulation;
• Fig. 5 shows a model for a stimulation pulse and a dissipation of the imposed pulse
• Fig. 6A shows an impedance model for a twelve-position electrode array in animal tissue
• Fig. 6B shows an exemplary driver configuration in a "can" for driving electrodes such as are portrayed above;
• Figs. 7A, 7B, and 7C show exemplary positioning of integrated circuitry chips relative to conductors of a lead;
• Fig. 8 shows an exemplary sensing arrangement using shield electrodes
• Fig. 9 A shows an exemplary drive mechanism for the use of currents to communicate sensed voltages
• Fig. 9B shows an exemplary sensing mechanism usable in a "can" for making use of currents such as portrayed in the previous figure;
• Fig. 9C shows an exemplary drive mechanism for the use of phase or frequency modulations to communicate sensed voltages
• Fig. 9D shows an exemplary drive mechanism for the use of modulation functions to communicate sensed voltages, and an exemplary demodulation mechanism usable in a "can" for making use of modulations such as portrayed in the previous figure.
• Figs 2A, 2B, 2C, 2D, and 2E show models for stimulation fields when various combinations of electrode selection and drive are employed.
• Fig. 2A shows an exemplary array 31 of twelve electrodes in a 3 by 4 rectangular layout.
• Fig. 2B models the situation when only two electrodes 32, 33 are energized, the other ten electrodes being permitted to "float" (at high impedance). In this figure it is assumed that the two driven electrodes are "floating", meaning that there is no particular "ground” reference (to body tissue) in the can 12.
• Equipotential lines 39, 38, 37 and equipotential lines 36, 35, 34 are expected to be fairly symmetrical. On one model the voltage at 36 has dropped to around 37 percent of the voltage at electrode 32, and the voltage at 35 has dropped to around 24 percent of the voltage at electrode 32.
• Fig. 2B As in the modeling of subsequent figures, the percentages are of course a function of assumptions about tissue conductivity and physical dimensions. The relative levels of signal depicted in the various figures are thought to be at least approximate indicators of the effects associated with various electrode configurations.
• Fig. 2C models the situation when electrodes 60, 61 are driven in one direction and electrode 62 is driven in the opposite direction. Again the other ten electrodes are at high impedance. In this figure it is assumed that the two drive levels are "floating", meaning that there is no particular "ground” reference (to body tissue) in the can 12.
• the equipotential lines of this figure are expected to be fairly symmetrical both on a vertical axis centered in the figure, and on a horizontal axis passing through electrode 62.
• the voltage at 52 has dropped to around 64 percent of the voltage at electrode 61
• the voltage at 53 has dropped to around 58 percent of the voltage at electrode 61.
• Fig. 2D models the situation when electrodes 71, 72 are driven in opposite directions, and when two shield electrodes 73, 74 define a shield potential relative to a node (omitted for clarity in Fig. 2D) about which more will be said below.
• the equipotential lines of this figure are expected to be fairly symmetrical both on a vertical axis centered in the figure, and on a horizontal axis centered in the figure.
• the voltage at 77 has dropped to around 9 percent of the voltage at electrode 71, and the voltage at 73 has dropped to zero.
• Fig. 2D which has shield electrodes tied to a node as will be discussed
• Figs. 2A, 2B, or 2C modeled results in Figs. 2A, 2B, or 2C
• Such stimulation might be deep brain stimulation, or spinal cord stimulation, or therapeutic stimulation for example for paralysis.
• Fig. 2E models the situation when electrodes 92, 93 are driven in opposite directions, and when ten shield electrodes 91 define a shield potential relative to a node (omitted for clarity in Fig. 2E) about which more will be said below.
• the equipotential lines of this figure are expected to be fairly symmetrical both on a vertical axis centered in the figure, and on a horizontal axis centered in the figure.
• the voltage at a point that is three or four electrode spacings away has dropped to around 0.07 percent of the voltage at a driven electrode, and the voltage at any shield electrode 91 has dropped to zero.
• the model suggests the voltage may drop to 0.02 percent of the drive voltage.
• a typical chip might be 1.4 by 3.0 millimeters, with electrodes sensing at a cellular level with spatial definition in the nature of 100 microns.
• Fig. 3 shows an exemplary crosspoint matrix (switching fabric) 124 that may be used in an integrated circuit chip according to an embodiment of the invention. Electrodes 112 through 123 are connected to this switching fabric. Leads Sl and S2 (comparable to conductors 15, 16 in Fig. IB) also appear and connect to the fabric. An exemplary switch 126, along with thirty-five other switches left unlabeled for clarity in Fig. 3, provides the switching of the fabric. As a matter of terminology we will sometimes say that a particular electrode is "enabled" to one of the columns of the fabric, meaning that it is connected thereto.
• each electrode such as 112 may be connected to Sl, to S2, or to node 111, or may be at a high impedance. Additional columns may be provided for fabric 124 to permit selective connection of an electrode to a sensing circuit, or to permit selective connection of two electrodes to respective inputs of a differential amplifier, as will be described below.
• the node 111 may be thought of as a "floating node" in the sense that it is not tied metallically to any power supply line but is at some intermediate level. The intermediate level may move upward or downward as required to dissipate drive (stimulation) signals.
• the electrodes together with the switching fabric may be conveniently be referred to as "multiplexed electrodes" in this context. Elsewhere in the discussion below, a multiplexing as between different integrated circuit chips (different electrode locations) may also be carried out.
• Node 111 is important because it can provide a common connection point for a plurality of shield electrodes, so that differing potentials nearby to distinct shield electrodes will tend to be equaled out. But node 111 is also important because it can be tied in a predefined way through circuitry 125 (about which more will be said below) to the conductors Sl, S2.
• Fig. 4 shows an arrangement 175 in which an exemplary selection of electrodes 132-141 serving as shield electrodes tied to a common node 146 and other electrodes 131, 142 providing sensing or stimulation.
• particular crosspoint switches fabric 124 in Fig. 3 are closed to bring about the connections such as 143 in Fig. 4.
• Common node 146 is like node 111 in Fig. 3.
• the active crosspoint connections are shown in Fig. 4, for clarity, and the other possible crosspoint connections are omitted for clarity.
• the circuitry 125 (Fig. 3) is composed of capacitors 144, 145 which define node 146 to fall about half way between conductors Sl, S2.
• the capacitors 144, 145 are matched or nearly matched in value.
• the arrangement 175 is able to bring about the results portrayed in Fig. 2E, where driven electrodes 131, 142 correspond to electrodes 92, 93 in Fig. 2E.
• Shield electrodes 132-141 correspond to shield electrodes 91 in Fig. 2E.
• Fig. 5 shows a model for a stimulation pulse and a dissipation of the imposed pulse, in a shielded arrangement such as discussed above.
• a pulse 161 may persist for half a microsecond, the pulse here being bipolar, with one driven electrode driven to slightly over two volts, and the other driven electrode pulled down to slightly less than minus two volts.
• the stimulus fades (as modeled by shape 162).
• the stimulus has faded nearly to nothing within five or six milliseconds. Later another pulse 163 may happen.
• Fig. 6A shows an impedance model for a twelve-position electrode array 31 in animal tissue. In this model it is assumed that electrodes 92, 93 are driven (as in Fig.
• Each of the driven electrodes 92, 93 is modeled as have some impedance 171, 172 through the adjacent tissue of the animal.
• Fig. 6B shows an exemplary driver configuration 205 in a "can" 12 for driving electrodes such as are portrayed above in circuitry 175 (Fig. 4).
• Positive-going drive and negative-going drive 177 are capacitively coupled (through capacitor 176) to the lead conductors Sl, S2 as shown.
• a reference 178 may be defined within the can 12, and in some applications might be tied to a metal housing of the can 12 and thus be coupled to the animal, although most of the teachings of the invention offer their benefits even if the point 178 is floating relative to everything else in the figure.
• Figs. 7A, 7B, and 7C show exemplary positioning of integrated circuitry chips relative to conductors of a lead.
• Fig. 7A shows a single IC chip O bonded to conductors 181 (for example conductors Sl, S2). A lumen 185 helps to guide the lead into place and may later be withdrawn.
• Fig. 7B shows two IC chips O, P bonded back- to-back to conductors 181 and tied together by physical material as shown.
• Fig. 7C shows four IC chips O, P, L, and F bonded in a square to conductors 181 and tied together by physical material as shown.
• the arrangement of Fig. 7 A provides (for example) 12 electrodes at each electrode position along the length of the lead.
• the arrangement of Fig. 7B provides 24 electrodes at each electrode position along the length of the lead.
• the arrangement of Fig. 7C provides 48 electrodes at each electrode position along the length of the lead.
• Fig. 8 shows an exemplary sensing arrangement 204 using shield electrodes 191. In this arrangement two particular electrodes 92, 93 (see again Fig. 2E) are connected with inputs of differential amplifier 192.
• the amplifier 192 has an output 193 which is communicated to electronics external to the electrode location (for example to can 12, omitted for clarity in Fig. 8).
• the node 111 is again tied to circuitry 125, which in this case provides a diode drop 194 away from one supply line Vss and is urged toward the other supply line Vcc by resistor 195.
• Vcc and Vss may be the same as, or may be derived from, lines Sl and S2.
• the switching fabric 124 (Fig. 3) will have two more columns, as discussed above in connection with Fig. 3.
• Onsite signal processing as described herein, can reduce noise.
• Fig. 9 A shows an exemplary drive mechanism 203 for the use of currents to communicate sensed voltages. Electrodes and differential amplifier are as in Fig. 8, but the amplified signal 193 drives a voltage-to-current converter 196, which in turn drives particular levels of current in the lines Sl, S2. This current is later sensed in the can 12 using, for example, the exemplary sensing mechanism 202 of Fig. 9B. The current passes through resistor 198 and the developed IR drop reaches differential amplifier 197.
• FIG. 9C shows an exemplary drive mechanism 201 for the use of phase or frequency modulations to communicate sensed voltages.
• a voltage-to-frequency converter 199 can drive current driver 196 to communicate sensed-data information by means of a frequency modulation.
• a phase modulation could be used.
• Fig. 9D shows an exemplary drive mechanism 207 for the use of modulation functions to communicate sensed voltages, and an exemplary demodulation mechanism 206 usable in a can 12 for making use of modulations such as portrayed in the previous figure.
• a modulation function f0 modulates at modulator 211.
• a demodulation mechanism uses demodulators 213, 214, 215 with the same functions f ⁇ , f 1, fn to derive distinct voltages, each of which is proportional to a sensed voltage such as at electrodes 92, 93.
• a method is carried out so as to apply an electrical pulse to, or to sense electrical activity at, a first region of tissue in an animal.
• a first array of electrodes is provided at the first region of tissue, the array disposed upon a respective surface.
• the first array comprises respective first and second electrodes disposed upon the respective surface.
• the first array further comprises a plurality of respective third electrodes (shield electrodes) also disposed upon the respective surface and surrounding the respective first and second electrodes.
• the first array of electrodes is electrically selectively connected via a lead to electronics located external to the first array of electrodes, such as the can 12.
• the lead comprises at least one electrical conductor and for example may have two conductors. Selective connections are made so that sensing or driving circuitry is connected to the first and second electrodes.
• the shield electrodes are configured to serve as an electrical shield for the first and second electrodes through conductive coupling with tissue nearby thereto.
• the surface carrying the electrodes can be substantially planar, if for example it is a surface of an integrated circuit.
• the surface would not have to be planar, however, and might for example be convex.
• the number of shield electrodes might be as few as two, might be six, and in the embodiments discussed herein the number of shield electrodes may be ten.
• the circuitry 125 at the common node 111 of the shield electrodes can bias the shield electrodes at a stable voltage between the positive and negative power supplies.
• the the stable voltage between the positive and negative power supplies may be defined to be at least a diode drop away from either of the power supplies.
• the circuitry may further establish the stable voltage at least two diode drops away from the potential of the substrate of the integrated circuit.
• Sensed electrical activity may be converted to a digital signal, the digital signal thereby carried on an electrical conductor or conductors of the lead to the electronics (for example can 12).
• an envelope modulation (AM) may be employed.
• addressing techniques are employed to permit carrying out stimulation at one location and later at a different location.
• Other techniques such as the multiplexing techniques mentioned above may be employed to permit sensing of electrical activity at each of two or more locations.
• the multiplexing may be for example time-domain multiplexing or frequency-domain multiplexing.
• One embodiment of the invention comprises the use of an array of multiplexed electrodes for applying an electrical pulse to, or for sensing electrical activity at, a region of tissue in an animal.
• a first array is provided at a first region of tissue.
• the multiplexing permits each electrode to be electrically isolated, connected to at least one conductor within the lead, or connected to a floating node connected to other electrodes in the array.
• Each electrode can likewise be electrically connected to at least one input of a sensing circuit.
• Each electrode can likewise be electrically connected to a current source.
• at least one electrode that is enabled to the floating node is adjacent to at least one electrode that is enabled to a conductor in the lead.
• at least one electrode that is enabled to the floating node is adjacent to at least one electrode that is enabled to an input of a sensing circuit.
• a first electrode can be enabled to a first conductor in the lead
• a second electrode can be enabled to a second conductor in the lead
• at least two additional electrodes on the surface are enabled to the floating node.
• the floating node 111 may be capacitively coupled to at least one conductor in the lead. Or the floating node may be capacitively coupled to two conductors in the lead using two substantially equivalent capacitors. Or the floating node may be electrically connected to at least one conductor in the lead and that conductor is electrically isolated from the drive circuitry.
• the floating node may be biased to be at least one diode drop away from sensor supply voltages. It will be appreciated that in use with animals, a medical carrier will typically comprise multiple such electrode arrays connected to said at least one conductor in the lead.
• a sequence of steps may be carried out in which a first value is stored that is indicative of the sensed phenomena. Later a second value is stored indicative of the sensed phenomena at a later time. The two values may be subtracted so that all that needs to be communicated is the difference between the two values.
• a typical sequence of steps may be to selecting first electrodes from an array for use to sense or stimulate, and selecting second shield electrodes from the array connected to a floating node, observing phenomena relating to the animal and noting the phenomena observed in connection with the selected electrodes.
• a different set of electrodes from the array are used to sense or stimulate, and fourth shield electrodes from the array are connected to a floating node, and again phenomena are observed relating to the animal and noting the phenomena observed in connection with the selected electrodes.
• some combination of electrodes may be selected and may be employed for some interval thereafter, and during the interval, sensing or stimulation may be carried out.
• the tissue may be neural tissue.
• a removable distal accelerometer or motion sensor may be used to help in the treatment of movement disorders such as Parkinson's or dystonia.
• shield electrodes 191 bias input electrodes 92, 93 and reduce common-mode signals, making input more sensitive to near-field signals and less sensitive to distant ones.
• the shield electrodes 191 are biased one or two diode drops 194 above the substrate 125 potential (or below the substrate 125 potential, if the substrate 125 is most positive.).
• This idea is to bias the shield electrodes 191 at a stable voltage between Vcc and Vss, ideally at least a diode drop from either.
• the shield electrodes 191 will then act to reduce the common-mode signal that reaches electrodes 92 and 93 as amplified by the differential amp 192.
• First Method of Conveying Sampled Analog Signals from Lead IC to the Can. Referring to Figure 9 A, what is shown is some of the circuitry disposed on the Lead IC 203.
• One differential amplifier 192 is selected at a time, then the potential difference between electrodes 92 and 93 is converted to a current signal proportional to that potential difference at output leads Sl and S2.
• FIG. 9B what is shown is some circuitry within the can.
• the circuit uses a current-controlled voltage source and is similar to existing talk-back circuits.
• the can may directly employ a current- to- digital converter.
• the signal is amplified 197 and converted to a current on the
• Lead IC 202 In the can, the current is sampled to extract the analog signal as the tissue impedance 198 varies while the voltage on S2 is held constant. The output voltage signal from the amp 197 is proportional to the voltage drop across 198.
• This method is similar to the Second Method described above, but is extended to multiple locations (satellites), each being time multiplexed.
• Each location's Sl and S2 leads are clocked. For example, assume eight locations at 1 kHz sampling. A 10-kHz signal (with out-of-phase, pulsating DC square- wave signals on S 1 and S2, respectively) is forced on S 1 and S2.
• a 10-kHz signal (with out-of-phase, pulsating DC square- wave signals on S 1 and S2, respectively) is forced on S 1 and S2.
• a different timeslot following a "start" command is pre-set on each Lead IC 202. Satellite 0 is assigned the first timeslot, Satellite 1 is assigned the second timeslot, etc.
• Each Lead IC 202 has a Power Regulator that actively rectifies the Sl and S2 voltage.
• the analog amplifiers 197 are enabled on each Lead IC 202 only when that Lead ICs 202 timeslot is enabled. Otherwise, the circuit works like that described in the Second Method discussed above. This methodology, however, necessarily results in a more complex can circuitry design, which is needed to track timeslots, etc. In addition, this method requires a "Start Analog Multiplex" command be used as an extension of an existing communication protocol.
• this method is a variation of the Third Method discussed above.
• the "noise" of the amplifier's 197 current consumption is eliminated.
• the current on leads S 1 and S2 equals the sum of the amplifier's 197 current draw and the forced current that is proportional to the sampled voltage.
• the total current drawn by the enabled Lead 1C 202 is proportional to the differential voltage across the sample.
• the amplifier 192 samples, amplifies, and holds the resulting voltage 193 on a capacitor. The amplifier 192 then shuts down, and the current on Sl and S2 is only the current through the Voltage-Controlled Current Source (VCCS).
• VCCS Voltage-Controlled Current Source
• each Lead IC 201 is given a dedicated frequency 199.
• the can provides a stable voltage across Sl and S2, but samples the current drawn through Sl an S2.
• each thus each Lead 1C 201 converts the amplified voltage into a frequency and then pulls a constant- amplified sinusoidal current through the VCCS with, for example, a sinusoid-like wave centered on the frequency. (However, a square wave can be acceptable as well.)
• the phase of the carrier wave is being modulated.
• These carrier frequencies would likely be related to the clocking frequency. For example, the frequency on Satellite 0, would be approximately 10 times the clock frequency, Satellite 1 would be approximately 11 times the clock frequency, etc.
• this embodiment is a variation of the Fifth Method described above.
• the frequency "broadcast" by each Lead IC is fixed.
• the amplitude pulled down by each Lead IC varies with the sampled signal.
• a lock-in amplifier (213, 214, 215, etc.) in the can for each frequency recovers each transmitted signal, either digitally or via multiple lock-ins.
• the frequency signals can take the form of a sinusoidal-like wave or as a square wave 211. f0 is approximately 1/10 of the clock carrier frequency.
• this embodiment is a variation of the Sixth Method in which each enabled Lead IC amplifies the signal as in the First Method described above, and employs an analog-to digital converter (ADC) to convert the voltage into a binary number. This number is then sent back to the Can using a variation of existing talk-back circuitry. For example, each Lead IC would be allocated a certain range of clock cycles, during which a given Lead IC transmits back to the can the data that had just been gathered.
• ADC analog-to digital converter
• the signals are amplified and converted to a digital signal on all Lead ICs.
• Satellite 0 communicates its data
• Satellite 1 communicates its data, etc.

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• Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Radiology & Medical Imaging (AREA)
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• Life Sciences & Earth Sciences (AREA)
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• Neurology (AREA)
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• Electrotherapy Devices (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)

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• 2009
  • 2009-10-06 JP JP2011536357A patent/JP2012508611A/ja not_active Withdrawn
  • 2009-10-06 WO PCT/US2009/059704 patent/WO2010056438A2/en not_active Ceased
  • 2009-10-06 US US12/595,033 patent/US8644919B2/en not_active Expired - Fee Related
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