Patent Grant
9549708
The present disclosure relates generally to field of interacting with biological tissue using electrical probes, and more particularly to interacting with a neurological target through the use of microelectrode probes.
Neural recording and neurostimulation are categories of medical devices that are used to interact electrically with tissue. In the case of neural recording, physiological measurements are performed of neurological tissue that can diagnose, or treat, a patient. In the case of neurostimulation, electric charge is transferred to the tissue in order to create a therapeutic outcome, or to generate a diagnosis. Neural recording and neurostimulation devices are used today in the cochlea, the retina, the peripheral nervous system, the spine, the brain, and other parts of the body.
In a particular application where both neural recording and neurostimulation are utilized, conductive electrodes are placed in contact with deep brain structures in order to treat certain neurological conditions. In the case of stimulating the Pedunculopontine Nucleus, for example, as described in U.S. Pat. No. 6,356,784, the therapy can treat the symptoms of Movement Disorders such as Parkinson's disease. In the case of stimulating Brodmann Area 25, for example, as described in U.S. Pat. No. 7,346,395, the therapy can treat the symptoms of Mood and Anxiety Disorders.
Generally, neural recording is performed in deep brain structures by surgically inserting conductive electrodes and amplifying neurological signals using external electronic equipment. Neurostimulation, is performed by surgically implanting conductive electrodes in the target, and using an implantable pulse generator to apply electrical signals to the conductive electrodes.
In some cases, such as described in U.S. Pat. No. 6,016,449, a system has been developed where both neural recording and neurostimulation functions are available in a single, long term implantable, device.
In most techniques, the electrodes used for neural stimulation that are placed in contact with tissue have been metallic, cylindrical, with very sharp distal ends. In most cases, they only contain one microelectrode, which severely limits the amount of physiological information that can be collected from the patient.
In other techniques, the electrodes used for neurostimulation that are placed in contact with tissue have been metallic, cylindrical, and relatively large in size (e.g., 1.27 mm in diameter and 1.5 mm in length). In most cases, there are four or eight cylindrical electrodes placed on a common axis. The stimulation methods are generally invasive, such as with the electrodes used in Deep Brain Stimulation, and the electrode lead is generally attached implantable pulse generator.
Furthermore, advances in micromachining technology have developed whole new applications for medical devices, and in particular, implantable devices such as for the treatment and diagnosis of neurological disorders.
Advances in the imaging of tissue have elucidated the function and anatomy of brain and nervous tissue, permitting the development of new therapies which include electrical stimulation methods. A number of research groups have reported on different approaches for imaging methods, and the construction of implantable devices to deliver therapies. The imaging methods are generally extra-corporeal, and involve large and/or sophisticated equipment such as Magnetic Resonance Imaging systems.
One of the great challenges for clinicians delivering electrical stimulation therapy is in localizing the correct location for electrode placement, and then confining the stimulation field to the appropriate anatomical target to deliver the therapy, without inducing side effects. Clinicians generally combine pre-operative navigational planning derived from Magnetic Resonance Imaging and/or Computed Tomography scan imaging systems, with intra-operative microelectrode recordings of electrophysiological phenomenon to find and locate the optimal target.
Volumes of anatomical interest are commonly found using microelectrode recording techniques which involve invasively inserting metal tips to find the area of interest by its electrophysiological activity. This may be uncertain, time consuming, and repetitive insertions may be hazardous to patient health.
Unfortunately, there are several limitations to current practice including uncertainty, discomfort for the patient, and a heavy financial burden to deliver the therapy. These factors can render the therapy less attractive to clinicians, patients and payers.
It would be a very useful advancement in the art of neural recording and neurostimulation device technology and in the practice of functional neurostimulation if the same device could image a volume of brain tissue, and stimulate the same volume of tissue with precision and safety.
There are many other medical applications for the present device, such as detecting malignant tissue within healthy tissue.
The present disclosure provides a design and method which permit the imaging of small volumes of tissue along with the capability of stimulating precise areas within the volume of tissue. The imaging method presents an advancement over conventional methods that have relied on expensive and low resolution systems. The stimulation method presents an advancement over conventional techniques which have not permitted the precise steering of electrical fields into the optimal tissue activation volume required to deliver effective therapy. Combined, the imaging and stimulation method offers, for the first time, precise and high resolution stimulation of tissue in specific areas and volumes.
The disclosed devices and methods have special applications in medical use, particularly in the treatment of neurological disorders. Embodiments provide an unprecedented resolution in the imaging of tissue volumes by detecting local differences in electrical characteristics. In this way, some embodiments provide an imaging device, which while invasive and constrained in use, is able to provide a highly accurate registration of the imaged volume. The image registration permits the identification of anatomical structures, their surfaces and volumes, and their electrical characteristics such as, but not limited to, permittivity and conductivity.
When combined with stimulation methods, the device permits stimulation within specific regions, surfaces, and volumes of the registered image. The presently disclosed devices and methods provide the clinician and/or surgeon a tool by which they can both visualize the tissue of interest, and stimulate specific areas within it. This greatly increases the accuracy and safety of a surgery along with an improvement in the chronic therapeutic effects of stimulation.
The use of localized tomographical imaging to determine implant location and stimulation volume is a unique and important advancement in the field of neurological devices. Following the present disclosure, for the first time, clinicians will be able to substantially decrease the uncertainty in device placement, and increase the specificity of the location of stimulation.
The techniques described herein enjoy a number of advantages over conventional techniques to image tissue. Conventional methods in imaging require expensive equipment installations and resolution is increased by high field strengths in the case of Magnetic Resonance Imaging, or high X-ray dosages in the case of Computed Tomography scans. These high fields are not compatible with implantable devices containing metallic features, and artifacts caused by devices translate to image drift, errors, or decreased resolution in the registered image.
By bringing the imaging device into contact with the volume of interest, and measuring local differences in electrical characteristics of the volume, the some embodiments provide for images of unprecedented resolution and fidelity.
Likewise, the techniques for stimulation described herein enjoy a number of advantages over conventional efforts to stimulate tissue in a highly localized manner Conventional methods rely on implantable devices with electrical leads often composed of cylindrical contacts, or metal tips. Most methods rely on stimulation volumes extending only outwards from the device, as in the case of a cylindrical device.
One possible approach to this issue is the use of smaller electrodes, in order to stimulate with greater precision. However, there are practical limitations in surgery which prevent the clinician from precisely targeting the intended region. The image registration is often performed before the surgery, and subsequently navigational software is used to plan the implant trajectory and location. One approach is to incorporate the MRI into the surgery, and perform intra-operative imaging, however, this is economically unviable in many hospitals, and the low field strengths required to maintain compatibility with the implanted devices limit the resolution which can be achieved. For example, a surgeon would implant a cylindrical electrode lead after finding and confirming the stereotactic co-ordinates of the target site. As a more specific example, a neurosurgeon might implant an electrode lead in the Subthalamic Nucleus (STN) to treat the symptoms of Parkinson's Disease. The surgeon might not be able to easily find the STN, and even more commonly, might not be able to locate the area within the STN that they seek to stimulate using electric current. Furthermore, if the clinician seeks to stimulate only a specific area, surface, volume, or population of neurons or fiber bundles in, around, or near the STN, it would not be possible using today's technology because of the size and geometry of existing electrode leads, which are considerably larger than the aforementioned targets.
The presently disclosed devices and methods greatly improve current practice without fundamentally changing the surgical procedures currently in use. As an example, a neurosurgeon targeting the STN would implant the device using stereotactic co-ordinates very close to the STN. The surgeon would then deploy the several prongs from the device into and around the STN. The imaging method would be performed, which would provide the surgeon with a highly localized and high resolution image of the volume of tissue within the prongs of the device. The image will consist of a 2D or 3D tomography of the volume of tissue. The image is constructed using the differences in electrical characteristics of the volume such as, but not limited to, conductivity, permittivity, conductivity and/or permittivity anisotropy. The image can therefore provide information about, but not limited to, the location and direction of fiber tracts, neural cell density, the interface between grey and white matter. The image is created using electrical impedance tomography techniques which involve a sequence of steps by which current is applied between two electrodes and a potential difference is preferably detected across two different electrodes, or the same electrodes. By repeating this procedure across all the electrodes in the periphery of the imaged volume, an image can be registered with the tomographic data using any one of a number of image reconstruction techniques and algorithms.
Once the image has been registered, and the clinician can visualize what the device's exact location is, electrical stimulation can be applied to specific areas of the volume using the principles of neurostimulation and the superposition of electric fields. The clinician can then steer the stimulation field, and the volume of tissue activation, to particular areas of the volume. For example, the image might display the interface between the surface of the STN and fibers that are projecting from it, or to it. The clinician can then choose to stimulate this surface and the volume of activation is directed there by combining signals from several electrodes on the device prongs.
As a result, a previously inaccessible region can be quickly located, and stimulated, thereby decreasing surgical times and increasing the efficacy of treatment. In contrast, conventional devices were limited by the geometrical arrangement and size of electrodes, and by the lack of simultaneous or in-situ imaging when stimulating.
Another serious limitation to conventional devices is post-implantation movement. A patient that is reacting positively to the stimulation therapy might experience a movement of their electrode after implantation and thus, an immediate decrease or full halt in efficacy and the possible introduction of side effects. With the present device, if a device shift occurs, the volume of interest can be re-imaged, and the stimulation volume can be re-directed to the proper region.
The presently described devices and methods benefit from the ability of modern microfabrication techniques to facilitate the construction of the device. Recent advances in surface micromachining permit various electrode geometries consisting of favorable materials such as Platinum and Platinum-Iridium to be manufactured. The electrode substrates can then be assembled onto cut cylindrical components which consist of the prongs of the device. This assembly is further contained in an implantable catheter from which the prongs would extend during surgery.
In one aspect, an implantable neurological probe is disclosed including: an elongated probe assembly; at least one protruding shafts arranged at the distal end of the elongated probe assembly; a plurality of microelectrode elements arranged on the surface of the protruding shafts; at least one electrical contact arranged proximally along the elongated probe assembly; and at least one electrical conductor in electrical communication between at least one of the microelectrode elements and the at least one electrical contact.
In some embodiments, the protruding shafts can be reversibly retracted within the elongated probe assembly. In some embodiments, the elongated probe shaft is configured for insertion into a human body using an accepted procedure for insertion of deep brain stimulation leads. In some embodiments, the diameter of the elongated probe assembly is between 1 mm and 3 mm.
In some embodiments, at least one of the plurality of microelectrode elements is a stimulating electrode and at least one of the plurality of microelectrode elements is a detecting electrode. In some embodiments, at least one of the plurality of microelectrodes elements is both a stimulating electrode and a detecting electrode.
In some embodiments, each microelectrode element is formed on a conductive film, and where each microelectrode element is embedded within two isolating substrates. In some embodiments, the microelectrode embedded substrate is formable into a cylindrical assembly. In some embodiments, the protruding shafts can be formed to bend radial from the longitudinal axis of the cylindrical assembly. In some embodiments, one of the protruding shafts is longitudinal and centered along the longitudinal axis of the cylindrical assembly. In some embodiments, the protruding shafts are stiffened by a supporting member. In some embodiments, the longitudinal protruding shaft is stiffened by a supporting member.
In another aspect, a method for finding a neurological target including: implanting a neurological probe within a vicinity of a neurological target site, the neurological probe including an elongated cylindrical member, a plurality of protruding shafts, a plurality of microelectrode elements on each protruding shaft, at least one electrical contact arranged proximally along the probe shaft, and at least one electrical conductor in electrical communication between at least one of the plurality of the microelectrode elements and the at least one electrical contact; retracting the protruding shafts within the elongated cylindrical member before surgical implantation; expanding the protruding shafts in the vicinity of the neurological target site following implantation; recording electrophysiological signals from the neurological target site using at least one of the microelectrode elements on at least one of the protruding shafts; and stimulating the neurological target using at least one of the microelectrode elements on at least one of the protruding shafts.
In some embodiments, the protruding shafts are retracted within the elongated cylindrical member using a flexible pull wire situated in a lumen of the elongated cylindrical member. In some embodiments, the protruding shafts are expanded from within the elongated cylindrical member using a rigid, or semi-rigid, push rod situated in a lumen of the elongated cylindrical member. In some embodiments, the act of positioning the distal end of the neurological probe includes recording neural activity detected by at least one of the plurality of microelectrode elements and repositioning the distal end of the neurological probe as required, until the recorded activity is indicative of the distal end of the elongated probe shaft being located sufficiently at the neurological target site.
In some embodiments, the act of positioning the distal end of the neurological probe includes stimulating neural activity by applying electrical signals to at least one of the plurality of microelectrode elements on at least one of the plurality of protruding shafts, performing a clinical evaluation of the efficacy on the stimulation site in the implanted patient, and repositioning the distal end of the neurological probe as required, until the patient's response is indicative of the distal end of the elongated probe shaft being located sufficiently at the neurological target site.
In some embodiments, the act of positioning the distal end of the neurological probe includes inhibiting neural activity by applying electrical signals to at least one of the plurality of microelectrode elements on at least one of the plurality of protruding shafts, performing a clinical evaluation of the efficacy on the inhibition site in the implanted patient, and repositioning the distal end of the neurological probe as required, until the patient's response is indicative of the distal end of the elongated probe shaft being located sufficiently at the neurological target site.
In another aspect, a method is disclosed for finding a neurological target including: implanting a neurological probe within a vicinity of a neurological target site, the neurological probe including an elongated cylindrical member, a plurality of protruding shafts, a plurality of microelectrode elements on each protruding shaft, at least one electrical contact arranged proximally along the probe shaft, and at least one electrical conductor in electrical communication between at least one of the plurality of the microelectrode elements and the at least one electrical contact; retracting the protruding shafts within the elongated cylindrical member before surgical implantation; expanding the protruding shafts in the vicinity of the neurological target site following implantation; applying an oscillating electric current between at least two of the microelectrode elements on at least one of the protruding shafts; and detecting an electric voltage between at least two of the microelectrode elements on at least one of the protruding shafts.
In some embodiments, the act of applying oscillating currents and detecting electric voltages is performed to image the electrical characteristics of the volume of neurological tissue between the protruding shafts.
In another aspect, an implantable neurological probe is disclosed including: an elongated shaft having a distal end and an internal lumen; a support cylinder slidingly disposed in only a distal portion of the internal lumen; a plurality of shafts coupled to the support cylinder and arranged to be selectively extended from the distal end of the elongated shaft; a plurality of microelectrode elements disposed on each of the plurality of shafts, the microelectrode elements including a planar substrate having an insulative layer and a plurality of conductive traces disposed on the insulative layer, a stylet removably disposed in the internal lumen and configured to contact the support cylinder to selectively extend the plurality of shafts during implantation; and a pull wire coupled to the support cylinder to selectively retract the support cylinder and plurality of shafts within the internal lumen.
Some embodiments include a push-pull rod which includes the pull wire and the stylet.
In some embodiments, the elongated shaft is configured for insertion into a human body using an accepted procedure for insertion of deep brain stimulation leads.
In some embodiments, the diameter of the elongated shaft is between 1 mm and 3 mm.
In some embodiments, at least one of the plurality of microelectrode elements is a stimulating electrode and at least one of the plurality of microelectrode elements is a detecting electrode. In some embodiments, at least one of the plurality of microelectrodes elements is both a stimulating electrode and a detecting electrode.
In some embodiments, each microelectrode element is formed on a conductive film, and where each microelectrode element is embedded within two isolating substrates.
In some embodiments, the microelectrode embedded substrate is formable into a cylindrical assembly.
In some embodiments, the protruding shafts can be formed to bend radially from the longitudinal axis of the cylindrical assembly.
In some embodiments, one of the protruding shafts extends and is centered along the longitudinal axis of the cylindrical assembly.
In some embodiments, the protruding shafts are stiffened by a supporting member. In some embodiments, the longitudinal protruding shaft is stiffened by a supporting member.
In another aspect, an implantable neurological probe is disclosed including: an elongated shaft having a distal end and an internal lumen; a plurality of shafts arranged to be selectively extended from the distal end of the elongated shaft; and a plurality of microelectrode elements disposed on each of the plurality of shafts, the microelectrode elements including a planar substrate having an insulative layer and a plurality of conductive traces disposed on the insulative layer. In some embodiments, the plurality of shafts define a substantially cylindrical volume when fully extended.
In some embodiments, the elongated shaft is configured for insertion into a human body using an accepted procedure for insertion of deep brain stimulation leads.
In some embodiments, the diameter of the elongated shaft is between 1 mm and 3 mm.
In some embodiments, at least one of the plurality of microelectrode elements is a stimulating electrode and at least one of the plurality of microelectrode elements is a detecting electrode.
In some embodiments, at least one of the plurality of microelectrodes elements is both a stimulating electrode and a detecting electrode. In some embodiments, each microelectrode element is formed on a conductive film, and where each microelectrode element is embedded within two isolating substrates. In some embodiments, the microelectrode embedded substrate is formable into a cylindrical assembly. In some embodiments, the protruding shafts can be formed to bend radially from the longitudinal axis of the cylindrical assembly. In some embodiments, one of the protruding shafts extends and is centered along the longitudinal axis of the cylindrical assembly. In some embodiments, the protruding shafts are stiffened by a supporting member. In some embodiments, the longitudinal protruding shaft is stiffened by a supporting member.
In another aspect, a method is disclosed for finding a neurological target including: implanting a neurological probe within a vicinity of a neurological target site, the neurological probe including: an elongated shaft having a distal end and an internal lumen; a support cylinder slidingly disposed in only a distal portion of the internal lumen; a plurality of shafts coupled to the support cylinder and arranged to be selectively extended from the distal end of the elongated shaft; a plurality of microelectrode elements disposed on each of the plurality of shafts, the microelectrode elements including a planar substrate having an insulative layer and a plurality of conductive traces disposed on the insulative layer, a stylet removably disposed in the internal lumen and configured to contact the support cylinder to selectively extend the plurality of shafts during implantation; and a pull wire coupled to the support cylinder to selectively retract the support cylinder and plurality of shafts within the internal lumen. In some embodiments, the method further includes: retracting the plurality of shafts within the internal lumen before surgical implantation; extending the plurality of shafts in the vicinity of the neurological target site following implantation; recording electrophysiological signals from the neurological target site using at least one of the microelectrode elements on at least one of the protruding shafts; and stimulating the neurological target using at least one of the microelectrode elements on at least one of the plurality of shafts.
In some embodiments, the method includes: after the acts of recording and stimulating, retracting the plurality of shafts within the internal lumen and removing the neurological probe from a subject.
In some embodiments, the protruding shafts are retracted using the pull wire. In some embodiments, the plurality of shafts are extended using the stylet. In some embodiments, the neurological probe includes a push-pull rod which includes the pull wire and the stylet
In some embodiments, the act of recording neurophysiological signals includes recording neural activity detected by at least one of the plurality of microelectrode elements and repositioning the distal end of the elongated shaft as required, until the recorded activity is indicative of the distal end of the elongated probe shaft being located sufficiently at the neurological target site.
Some embodiments include stimulating neural activity by applying electrical signals to at least one of the plurality of microelectrode elements on at least one of the plurality of shafts, performing a clinical evaluation of the efficacy on the stimulation site in the implanted patient, and repositioning the distal end of the elongated shaft as required, until the patient's response is indicative of the distal end of the elongated shaft being located sufficiently at the neurological target site.
Some embodiments include inhibiting neural activity by applying electrical signals to at least one of the plurality of microelectrode elements on at least one of the plurality of shafts, performing a clinical evaluation of the efficacy on the inhibition site in the implanted patient, and repositioning the distal end of elongated shaft as required, until the patient's response is indicative of the distal end of the elongated shaft being located sufficiently at the neurological target site.
In another aspect, a method is disclosed for finding a neurological target including: implanting a neurological probe within a vicinity of a neurological target site, the neurological probe including: an elongated shaft having a distal end and an internal lumen; a support cylinder slidingly disposed in only a distal portion of the internal lumen; a plurality of shafts coupled to the support cylinder and arranged to be selectively extended from the distal end of the elongated shaft; a plurality of microelectrode elements disposed on each of the plurality of shafts, the microelectrode elements including a planar substrate having an insulative layer and a plurality of conductive traces disposed on the insulative layer, a stylet removably disposed in the internal lumen and configured to contact the support cylinder to selectively extend the plurality of shafts during implantation; and a pull wire coupled to the support cylinder to selectively retract the support cylinder and plurality of shafts within the internal lumen. Some embodiments include retracting the plurality of shafts within the internal lumen before surgical implantation; expanding the plurality of shafts in the vicinity of the neurological target site following implantation; applying an oscillating electric current between at least two of the microelectrode elements on at least one of the plurality of shafts; and detecting an electric voltage between at least two of the microelectrode elements on at least one of the plurality of shafts.
Some embodiments include: after the act of detecting, retracting the plurality of shafts within the internal lumen and removing the neurological probe from a subject.
Some embodiments include imaging the electrical characteristics of the volume of neurological tissue between the plurality of shafts based on the applied oscillating electric current and the detected electric voltage.
In some embodiments, the neurological probe includes a push-pull rod which includes the pull wire and the stylet.
In another aspect, a method for finding a neurological target including: implanting a neurological probe within a vicinity of a neurological target site, the neurological probe including: an elongated shaft having a distal end and an internal lumen; a plurality of shafts arranged to be selectively extended from the distal end of the elongated shaft; and a plurality of microelectrode elements disposed on each of the plurality of shafts, the microelectrode elements including a planar substrate having an insulative layer and a plurality of conductive traces disposed on the insulative layer, where the plurality of shafts define a substantially cylindrical volume when fully extended. In some embodiments, the method includes: retracting the plurality of shafts within the internal lumen before surgical implantation; extending the plurality of shafts in the vicinity of the neurological target site following implantation; recording electrophysiological signals from the neurological target site using at least one of the microelectrode elements on at least one of the protruding shafts; and stimulating the neurological target using at least one of the microelectrode elements on at least one of the plurality of shafts.
In some embodiments, the protruding shafts are retracted using a pull wire. In some embodiments, he plurality of shafts are extended using a stylet. In some embodiments, the neurological probe includes a push-pull rod which includes the pull wire and the stylet.
In some embodiments, the act of recording neurophysiological signals includes recording neural activity detected by at least one of the plurality of microelectrode elements and repositioning the distal end of the elongated shaft as required, until the recorded activity is indicative of the distal end of the elongated probe shaft being located sufficiently at the neurological target site.
Some embodiments include: after the acts of recording and stimutating, retracting the plurality of shafts within the internal lumen and removing the neurological probe from a subject
Some embodiments include stimulating neural activity by applying electrical signals to at least one of the plurality of microelectrode elements on at least one of the plurality of shafts; performing a clinical evaluation of the efficacy on the stimulation site in the implanted patient; and repositioning the distal end of the elongated shaft as required, until the patient's response is indicative of the distal end of the elongated shaft being located sufficiently at the neurological target site.
Some embodiments include inhibiting neural activity by applying electrical signals to at least one of the plurality of microelectrode elements on at least one of the plurality of shafts, performing a clinical evaluation of the efficacy on the inhibition site in the implanted patient, and repositioning the distal end of elongated shaft as required, until the patient's response is indicative of the distal end of the elongated shaft being located sufficiently at the neurological target site.
In another aspect, a method for finding a neurological target including: implanting a neurological probe within a vicinity of a neurological target site, the neurological probe including: an elongated shaft having a distal end and an internal lumen; a plurality of shafts arranged to be selectively extended from the distal end of the elongated shaft; and a plurality of microelectrode elements disposed on each of the plurality of shafts, the microelectrode elements including a planar substrate having an insulative layer and a plurality of conductive traces disposed on the insulative layer, where the plurality of shafts define a substantially cylindrical volume when fully extended. Some embodiment include retracting the plurality of shafts within the internal lumen before surgical implantation; expanding the plurality of shafts in the vicinity of the neurological target site following implantation; applying an oscillating electric current between at least two of the microelectrode elements on at least one of the plurality of shafts; and detecting an electric voltage between at least two of the microelectrode elements on at least one of the plurality of shafts.
Some embodiments include imaging the electrical characteristics of the volume of neurological tissue between the plurality of shafts based on the applied oscillating electric current and the detected electric voltage.
Some embodiments include: after the act of detecting, retracting the plurality of shafts within the internal lumen and removing the neurological probe from a subject
Various embodiments may include any of the above described elements or steps alone, or in any suitable combination.
The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views.
Described herein are microelectrode array devices, and methods of fabrication and use of the same, to provide highly localized and efficient electrical stimulation of a neurological target, such as individual neurons, groups of neurons, and neural tissue as may be located in an animal nervous system, such as deep within a human brain. In small, difficult to find brain targets such as the Pedunculopontine Nucleus, or in targets that requires highly localized levels of neural stimulation, such as the Subthalamic Nucleus, many microelectrodes are required in the brain region to find the target using electrophysiological recording. A higher number of microelectrodes will increase the chance of finding the neurons required for therapeutic stimulation. The microelectrode, or group of microelectrodes, that are closest to the target brain region will be used for chronic, therapeutic stimulation or inhibition.
The stimulation can be highly localized, because the microelectrode elements can be as small as only 2 μm or large as 2 mm in either of diameter or width. The relative spacing between such microelectrode elements can also be as small as only 2 μm or as large as 2 mm Generally, microelectrodes of about 150 μm in diameter, with about a 1000 μm spacing are particularly efficient in stimulating neural tissue.
An array of such microelectrode elements may consist of one or more such elements (e.g., sixteen elements), each disposed at a respective position, or site. This is in contrast to currently available stimulation leads, such as the Model 3387 or Model 3389 DBS leads commercially available from Medtronic, Inc. of Minneapolis, Minn. Such commercially available devices include relatively large, cylindrical electrodes measuring about 1.5 mm in height, and having a maximum of only four electrodes in use today for deep brain stimulation.
Smaller microelectrode elements can be used to provide neurological stimulation that is highly localized and efficient because an array of such microelectrodes can also be used to identify the stimulation region of interest. For example, one or more microelectrode elements of such an array of microelectrode elements can be used to record neuronal activity in the vicinity of the detecting/recording microelectrode elements. Such refinement offered by the relatively small size and/or spacing of the microelectrode elements can be used to obtain a highly localized map of neuronal activity in the region surrounding the implant. A suitably dimensioned microelectrode array having multiple microelectrode elements positioned in a general vicinity of a neurological target, can be used to locate a precise neurological target without further repositioning, by identifying those one or more microelectrode elements located in a very specific region of the neurological target. The microelectrode array can be programmed to stimulate in a very specific region, for example, using only a certain number of the microelectrode elements to actively stimulate the surrounding neurons and/or neuronal tissue, while other electrode elements of the array remain inactive.
In the embodiments described, the microelectrode arrays are positioned in three dimensional space. This has been a previous limitation of such microelectrode devices, which were usually implement in linear arrays, or two dimensional arrays on films. In the present embodiment microelectrode arrays are positioned along shafts which radiate from a central lumen, in order to cover as much volume in the target region with microelectrode arrays.
In some embodiments, an elongated device including such microelectrode arrays having elements with relatively small size and/or spacing can be used to obtain a highly localized map of neuronal activity in the region surrounding the implant. For example, such a device configured with a linear array of microelectrodes positioned along a length of a distal end of the device can be placed into a patient's brain. Preferably, the elements of the microelectrode array envelop a region including the neurological target. Neurological activity can then be independently detected by one or more of the microelectrode elements. The detected activity may be captured in a recorder or display device, allowing a clinician to identify which one or more of the microelectrode elements is positioned closest to the intended target. Knowing a respective location of each of the microelectrode elements along the device, and determining the distance to a reference, such as the patient's skull, a precise location of the target can be determined as the distance along a trajectory of the device, measured from the reference to the particular microelectrode element. Beneficially, location of the target can be determined without any repositioning of the elongated device, thereby simplifying the medical procedure and reducing patient risk.
In some embodiments, the device is for acute intra-surgical use, being removed after the target has been located, being replaced with a chronic probe, positioned at the determined target location. Alternatively or in addition, the device itself can be left in place as a chronic device, the same microelectrodes, or different ones, being used to record and/or stimulate the neurological target over an extended period.
One embodiment of a microelectrode device illustrated in
The microelectrode lead assembly 100 is preferably sized and shaped for its intended neurological application. For example, the microelectrode lead assembly 100 may be at least partially placed within the central nervous system. Alternatively or in addition, the microelectrode lead assembly 100 may be at least partially placed within other parts or organs of the body, such as the epidural space of the spine, or other locations within the peripheral nervous system, or within an organ such as the liver or heart. Thus the diameter and length of the microelectrode lead assembly 100 may vary depending on the particular anatomical target. Additionally, the configuration of the microelectrode array shafts 160 is also sized and shaped for an intended neurological target. The number, shape, orientation, size, and spacing of the microelectrode elements of the array can be defined in response to the intended neurological target.
In at least some embodiments one or more of the microelectrode elements are sized and or spaced to record from and/or stimulate neurons. The microelectrode lead assembly 100 can be used to detect and/or record neuronal activity at the neurological target. Neuronal activity naturally occurring within the neurological target gives rise to local electromagnetic fields that can be detected by one or more of the microelectrode elements of the microelectrode array. For example, electric fields produced by neurons will polarize one or more of the microelectrode elements. Such polarization gives rise to an electrical potential with respect to a reference, such as electrical ground, or another one of the microelectrode elements. Such electric activity can be further conducted to one or more of the cylindrical contacts 106 through the internal electrical conductors. One or more of the cylindrical contacts 106, in turn, can be connected to one or more additional medical devices for further processing of the detected electrical activity. For example, the cylindrical contacts 106 can be coupled to a display device or recording device for displaying and/or recording electrical activity from the neurological target.
Alternatively or in addition, one or more of the microelectrode elements can be used to electrically stimulate the neurological target. For example, one or more externally generated electrical signals can be applied to one or more of the cylindrical contacts 106. These electrical signals can be conducted through the internal electrical conductors to one or more of the microelectrode elements of the microelectrode array. Depending on the amplitude and polarity of the electrical signals, an electrical field will be induced by the polarized microelectrode elements. Electrical fields induced by such polarization can interact with one or more neurons at the neurological target.
Alternatively or in addition, one or more of the microelectrode elements can be used to perform Electrical Impedance Tomography of a neurological target or other bodily organ. For example, one or more externally generated electrical signals can be applied as a current to one or more of the microelectrode elements. Depending on the physiological characteristics of the tissue being imaged, and depending on the frequencies of the current signals applied, an electrical field will be induced in the tissue. Electrical fields induced by such polarization can be detected by other microelectrode elements, thereby creating a localized image of conductivity, permittivity, and/or other electrical characteristics.
Mechanical components of the implantable neurological lead assembly 100 include the elongated outer cylindrical member 102, which can be a simple polymeric cylinder, or a rigid metallic or rigid polymeric cylinder. The outer cylindrical member 102 can vary in length and diameter but is generally at least about 28 cm long, (e.g., at least 20 cm long, at least 25 cm long, at least 28 cm long, at least 30 cm long, etc.) and around 1.27 mm in diameter (e.g., in the range of 1.0-2.0 mm in diameter).
The neurological lead 100 can be implanted near a neurological target, such as a target brain structure, using common neurosurgical techniques such as stereotaxy or endoscopy. The microelectrode lead assembly 100 can be inserted in its retracted state without support, or within a supporting cannula having an inner dimension slightly larger than the outer dimension of the device. The cannula, when used, would be removed once the microelectrode lead assembly 100 has been suitably positioned. In some embodiments a lumen along the axis of the outer cylindrical member 102 permits the insertion of a rigid stylet which renders the microelectrode lead assembly 100 rigid during surgical implantation. This is particularly helpful during insertion, positioning and repositioning of flexible embodiments of the microelectrode lead assembly 100. The stylet is removed after implantation leaving the probe in its surgical target. In some embodiments the stylet is also a rigid push rod, which is used to expand the microelectrode array shafts 160 into the tissue. In some embodiments, the microelectrode lead assembly 100 contains a flexible pull wire which is used to pull the microelectrode array shafts 160 back into the retracted position. In yet additional embodiments, the microelectrode lead assembly 100 contains only one rigid push-pull rod which is used to both push and pull the microelectrode array shafts 160 in its expanded and retracted position respectively. In yet additional embodiments, where the microelectrode lead assembly 100 is not intended to remain in the patient's brain after surgery, the rigid push-pull rod may be permanently attached to the microelectrode array shafts 160.
A clinician can connect one or more of the microelectrode elements to a display unit or a recording unit through the cylindrical contacts 106. The recording unit, not shown, allows a clinician to identify certain regions of the brain according to their electrical activity. In some embodiments, such recording information can be processed automatically, through the use of a suitably programmed computer processor. The electrodes used to record from the brain can be the same electrodes as those used to stimulate tissue. The recording electrodes can also be separate from those used to stimulate the brain. This situation might be preferred because electrodes destined for recording may be different in size and design than those for stimulation.
The operator can connect the electrodes to an external stimulation source or an implantable source. In either instance, the source can include a pulse generator for applying signals to the electrode sites. The signals from such a pulse generator can be connected directly to the electrodes, or they can be preprocessed using electronics embedded in the device. The electronics can filter certain parts of the original signal. If there are more electrodes than signals, the electronics can route or otherwise interconnect the stimulation source as necessary.
A perspective view of the portion of a human anatomy is illustrated in
Referring now to
As illustrated, one or more of the microelectrode elements 145 of the microelectrode probe assembly 140 are positioned in intimate contact with the neurological target 149. In more detail, each microelectrode element 145 is a disc electrode along a shaft. It is understood that some microelectrode array shafts 141 can be in contact with the neurological target, while other microelectrode array shafts 141 are not (as shown). Additionally, it is understood that some microelectrode elements 145 can be in contact with the neurological target, while other microelectrode elements 145 are not (as shown). In at least some embodiments, one or more of the microelectrode elements 145 are remotely accessible from a proximal end of the probe assembly 140 via one or more electrically conductive leads (not shown).
In at least some embodiments, selectable microelectrode elements 145 can be activated to record and or stimulate the target 149. For example, recordings of neurological activity from microelectrode elements 145 in contact with the target 149 can be used to identify the location of the target 149 relative to the probe assembly 140 or relative to a standard stereotactic reference coordinate. As determined form the recordings, only those microelectrode elements 145 in contact with the target may be activated to stimulate the target.
Any of the supporting structures described herein, such as the supporting structure 140 illustrated here can be a ridged, or semi rigid structure, such as a polymeric cylinder. Alternatively or in addition, the structure can be a flexible structure, such as one or more flexible substantially non conducting substrate (i.e., a bi-electric ribbon) onto which the microelectrode elements 145 are formed as electrically conductive film layers. The one or more microelectrode elements 145 are in communication with electronic circuitry (not shown) through one or more electrical leads (not shown) that can be routed through an internal lumen of a supporting structure 140 and/or formed using elongated film layers along a flexible, ribbon like supporting structure 140.
In some embodiments, the microelectrode elements 145 can be placed into the brain generally for recording and/or stimulation of the cortex and for deep brain stimulation and/or recording of neurological targets including the subthalamic nucleus and the pedunculopontine nucleus. The microelectrode elements 145 can also be placed in other parts of the body, such as the spine, the peripheral nervous system for neural recording and/or neural stimulation of such portions of an animal anatomy. Although microelectrodes are discussed generally throughout the various embodiments, there is no intention to limit the upper or lower size of the microelectrodes. The devices and methods described herein are generally scalable, with a microelectrode size determined according to the intended application. For at least some of the neurological applications, microelectrodes are dimensioned sub-millimeter. In some embodiments, the microelectrodes are formed as planar structures having a diameter of about 150 μm that are arranged in a linear array with center to center spacing of about 1000 μm. The planar structure of the microelectrodes can have regular shapes, such as circles, ellipses, polygons, irregular shapes, or a combination of such regular and/or irregular shapes.
This probe assembly 140 is implantable near a neurological target, such as a target brain structure, using common neurosurgical techniques such as stereotaxy or endoscopy. The device might be inserted without support or within a cannula which may have an inner dimension slightly larger than the outer dimension of the device. Alternatively, or in addition to, the device may have a rigid stylet running along its central axis with an outer diameter that is smaller than the inner diameter of an axial lumen in the device. When used, such a cannula, or a stylet, is generally retracted once the device is in position.
The operator can connect the probe assembly 140 to a recorder unit configured to identify certain regions of the neurological target (e.g., the brain) according to the electrical activity detected by the probe assembly 140. In some embodiments, the microelectrode elements 145 used to record from the neurological target 149 can be the same microelectrodes as those used to stimulate the target in applications in which both recording and stimulation are accomplished. Alternatively or in addition, the microelectrode elements 145 used to record from the neurological target 149 can be separate microelectrode elements 145 from those used to stimulate the target 149. In some embodiments, microelectrodes destined for recording (e.g., 145) may differ in one or more of size, shape, number, and arrangement from those microelectrodes destined for stimulation, e.g., using different microelectrodes.
The microelectrode elements 145 configured for stimulation can be connected to a stimulation source through one or more interconnecting leads. In some embodiment, at least a portion of the stimulation source can be extracorporeal. Alternatively or in addition, the stimulation source can be in vivo. Any implanted elements of the stimulation source are preferably fabricated and/or contained with a hermetically sealed, bio-compatible envelope. Such bio-compatible packaging of signal sources is well known, for example, in the area of artificial pacemakers. The stimulation source, when provided, may be a controllable signal generator producing a desired signal according to a prescribed input. For example, the signal generator may receive an input indicative of a desired output stimulation signal frequency. Such output stimulation signals can have a variety of wave forms, such as pulses, charged balanced pulses, sinusoidal, square wave, triangle wave, and combinations of such basic wave forms.
In some embodiments, the stimulation source includes a pulse generator for applying signals to the microelectrodes site. The signals from the pulse generator can be connected directly to the microelectrodes, or they can be preprocessed using electronics. In some embodiments, such preprocessing electronics are embedded within the implantable device. The preprocessing electronics can filter certain parts of an original signal, such as a cardiac pacemaker signal, in order to select preferred frequency components of the original signal that are at or near a peak resistance frequency of the microelectrodes. For embodiments in which there are more microelectrodes than signals, electronics can route the stimulation signals to preferred one or more of the microelectrodes.
Referring now to
Referring now to
Referring now to
The microelectrode lead assembly 100 contains one removable rigid push rod 170, and one non-removable flexible pull wire 175. The rigid push rod 170 is used to expand the microelectrode array assembly 150 into its expanded state. The flexible pull wire 175 is used to pull the microelectrode array assembly 150 back into is retracted state. As shown, the rigid push rod 170 is composed of three features. The first feature is a hollow rigid stylet 172 that is also used to straighten the microelectrode lead assembly 100 during implantation. The second feature is a longitudinal slit 173 which permits access to the central lumen of the rigid stylet 172. The third feature is the push handle 174 which permits the operator to apply a pressure and expand the microelectrode array assembly 150 at the distal end. As shown, the flexible pull wire 175 has three features. The first feature is a flexible central wire 176 which is permanently attached to the microelectrode array assembly 150 at the distal end. The second feature is a pull handle 178 which the operator can use to retract the microelectrode array assembly at the distal end by pulling. The third feature is a hole 179 in the pull handle 178 which the operator can use to facilitate the pulling action required of the component. Together, push rod 170 and pull rod 175 are used in order to expand and retract the microelectrode array shafts 160 and the distal end of the microelectrode lead assembly 100.
Referring now to
The next feature on the microelectrode array film 200 is the distal structural cylinder 210 which is shown in its flattened state, but once assembled will be used to stabilize the film in its final assembly. The microelectronic platform 212 is where a subsequent microelectronic component will be attached. The microelectronic component is explained in detail below. It is preferably attached to the microelectrode array film 200 while it is still in its flattened state. On the microelectronic platform 212 are arranged the microelectronic platform bond bands 270 which are used to electrically communicate the microelectrode elements 265 to external equipment through the microelectronic component. They are arranged in a two dimensional array. The central structural cylinder 214 which is shown in its flattened state, but once assembled will be used to stabilize the film in its final assembly. The helical ribbon cable 216 which is shown in its flattened state, but once assembly will be used to permit movement of the microelectrode array assembly 150 within the microelectrode lead assembly 100. The proximal structural cylinder 218 is shown in its flattened state, but will be attached to an internal cylinder within the microelectrode lead assembly 100 and is the only non-moving part of the microelectrode array film 200. On the proximal structural cylinder 218 are the proximal contact pads 208 which are used to communicate the elements of the microelectronic component to lead wires that communicate the distal portion of the microelectronic lead assembly 100 to its proximal portion.
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
When the microelectrodes are in use, they are placed on the same plane, in order to improve the operator's understanding of anatomical placement of the electrophysiological recording, and or stimulation.
In some embodiments the protruding shafts may be curved, or bent, into a different angle. This may have the advantage that the tips of the protruding shafts can cover a greater volume.
In some embodiments it is advantageous for the protruding shafts to be bent in such a manner that when in the expanded state, they remain parallel to the longitudinal axis of the elongated probe. The alternative embodiment of a distal microelectrode assembly 650 shown in
In some embodiments it is advantageous for the microelectrode array film to be positioned on the exterior of the protruding shafts.
In some embodiments it is advantageous to include protruding shafts and different distal distances along the longitudinal axis of the elongated microelectrode probe.
In some embodiments it is advantageous to not require a microelectronic element 300. This may be the case when using the embodiment in a stimulation mode only, or when using low numbers of stimulation sites.
In some embodiments it is advantageous to not require that the protruding shafts be rigid, and therefore they do not need to be supported. This may be the case when using the embodiment in delicate tissues.
Microelectronic Elements
When the embodiment is in used only for neural recording, the microelectronic element 300 may be configured to only collect electrophysiologically recorded data.
When the embodiment is in used only for neural stimulation, the microelectronic element 300 may be configured to only generate, or alternatively route, stimulation signals.
In some embodiments the operator wishes to record and stimulate with the same microelectrode elements. To perform this method microelectronic element 300 may be implemented with both recording and stimulation functions.
Stimulation signals are used to stimulate or inhibit neuronal activity and the neuronal recording and stimulation microelectronic circuit 350 can perform the generation, or routing, of stimulation signals. The microelectrode element 365 chosen to apply the stimulation signal can be selected using switchbox 351. In some embodiments, several switches are chosen in order to apply the same signal to several microelectrode elements 365. Additionally, switchbox 357 can be in the stimulation state. In some embodiments, several unique signals are generated, or routed, and applied to at least one microelectrode element 365. If the stimulation signal is generated outside of the microelectronic element 300, the signal can be conditioned, and if necessary amplified, using signal conditioner 355. A dedicated lead wire on microelectrode lead assembly 100 can be reserved for this purpose. Additionally, some embodiments may include high-pass filters 360, of which each filter is dedicated to an individual microelectrode element 365, or shared between several microelectrode elements 365. These high-pass filters 360 may be used in order to tune the stimulation signal to the peak resistance frequency of the microelectrode element 365.
Additionally, dedicated lead wires on microelectrode lead assembly 100 can be reserved for supplying power to the neural recording and stimulation microelectronic element 350, clock signals, and ground, and command signals, recorded signals, and stimulation signals.
Electrical Impedance Tomography
Various embodiments of micro-fabricated neurostimulation devices have been described herein. These embodiments are giving by way of example and are not intended to limit the scope of the present invention. It should be appreciated, moreover, that the various features of the embodiments that have been described may be combined in various ways to produce numerous additional embodiments. Moreover, while various materials, dimensions, shapes, implantation locations, etc. have been described for use with disclosed embodiments, others besides those disclosed may be utilized without exceeding the scope of the invention.
Although some devices described herein are identified as either acute or chronic, it is understood that the device may be used acutely, or chronically. They may be implanted for such periods, such as during a surgery, and then removed. They may implanted for extended periods, or even indefinitely. Similarly, any devices described herein as being chronic, it is understood that such devices may also be used acutely.
The present disclosure is not to be limited in terms of the particular embodiments described in this application, which are intended as illustrations of various aspects. Many modifications and variations can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is to be understood that this disclosure is not limited to particular methods, reagents, compounds compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.
With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.
It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”
In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.
As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.
One or more or any part thereof of the techniques described herein can be implemented in computer hardware or software, or a combination of both. The methods can be implemented in computer programs using standard programming techniques following the method and figures described herein. Program code is applied to input data to perform the functions described herein and generate output information. The output information is applied to one or more output devices such as a display monitor. Each program may be implemented in a high level procedural or object oriented programming language to communicate with a computer system. However, the programs can be implemented in assembly or machine language, if desired. In any case, the language can be a compiled or interpreted language. Moreover, the program can run on dedicated integrated circuits preprogrammed for that purpose.
Each such computer program is preferably stored on a storage medium or device (e.g., ROM or magnetic diskette) readable by a general or special purpose programmable computer, for configuring and operating the computer when the storage media or device is read by the computer to perform the procedures described herein. The computer program can also reside in cache or main memory during program execution. The analysis, preprocessing, and other methods described herein can also be implemented as a computer-readable storage medium, configured with a computer program, where the storage medium so configured causes a computer to operate in a specific and predefined manner to perform the functions described herein. In some embodiments, the computer readable media is tangible and substantially non-transitory in nature, e.g., such that the recorded information is recorded in a form other than solely as a propagating signal.
In some embodiments, a program product may include a signal bearing medium. The signal bearing medium may include one or more instructions that, when executed by, for example, a processor, may provide the functionality described above. In some implementations, signal bearing medium may encompass a computer-readable medium, such as, but not limited to, a hard disk drive, a Compact Disc (CD), a Digital Video Disk (DVD), a digital tape, memory, etc. In some implementations, the signal bearing medium may encompass a recordable medium, such as, but not limited to, memory, read/write (R/W) CDs, R/W DVDs, etc. In some implementations, signal bearing medium may encompass a communications medium such as, but not limited to, a digital and/or an analog communication medium (e.g., a fiber optic cable, a waveguide, a wired communications link, a wireless communication link, etc.). Thus, for example, the program product may be conveyed by an RF signal bearing medium, where the signal bearing medium is conveyed by a wireless communications medium (e.g., a wireless communications medium conforming with the IEEE 802.11 standard).
It is to be understood that any of the signals and signal processing techniques may be digital or analog in nature, or combinations thereof.
While certain embodiments of this invention have been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.
The present application is a U.S. National Stage of PCT International Application Number PCT/EP2011/055045, filed Mar. 31, 2011, which claims priority to U.S. Provisional Application Ser. No. 61/320,089 filed Apr. 1, 2010, the entire contents of the foregoing applications are incorporated by reference herein.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP2011/055045 | 3/31/2011 | WO | 00 | 12/14/2012 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2011/121089 | 10/6/2011 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 4245645 | Arseneault et al. | Jan 1981 | A |
| 4550733 | Liss et al. | Nov 1985 | A |
| 4837049 | Byers et al. | Jun 1989 | A |
| 4917093 | Dufresne et al. | Apr 1990 | A |
| 4928297 | Tsutsui et al. | May 1990 | A |
| 4969468 | Byers et al. | Nov 1990 | A |
| 4989617 | Memberg et al. | Feb 1991 | A |
| 5215088 | Normann et al. | Jun 1993 | A |
| 5391250 | Cheney et al. | Feb 1995 | A |
| 5400784 | Durand et al. | Mar 1995 | A |
| 5419777 | Hofling | May 1995 | A |
| 5496369 | Howard, III | Mar 1996 | A |
| 5524338 | Martyniuk | Jun 1996 | A |
| 5628317 | Starkebaum et al. | May 1997 | A |
| 5643330 | Holsheimer et al. | Jul 1997 | A |
| 5679355 | Alexander et al. | Oct 1997 | A |
| 5683422 | Rise | Nov 1997 | A |
| 5697651 | Fernandes | Dec 1997 | A |
| 5697975 | Howard et al. | Dec 1997 | A |
| 5702429 | King | Dec 1997 | A |
| 5713922 | King | Feb 1998 | A |
| 5713923 | Ward et al. | Feb 1998 | A |
| 5716377 | Rise et al. | Feb 1998 | A |
| 5727552 | Ryan | Mar 1998 | A |
| 5752979 | Benabid | May 1998 | A |
| 5755759 | Cogan | May 1998 | A |
| 5782798 | Rise | Jul 1998 | A |
| 5792186 | Rise | Aug 1998 | A |
| 5797970 | Pouvreau | Aug 1998 | A |
| 5800474 | Benabid et al. | Sep 1998 | A |
| 5800535 | Howard, III | Sep 1998 | A |
| 5814092 | King | Sep 1998 | A |
| 5824029 | Weijand et al. | Oct 1998 | A |
| 5833709 | Rise et al. | Nov 1998 | A |
| 5833714 | Loeb | Nov 1998 | A |
| 5843148 | Gijsbers et al. | Dec 1998 | A |
| 5893883 | Torgerson et al. | Apr 1999 | A |
| 5913882 | King | Jun 1999 | A |
| 5921924 | Avitall | Jul 1999 | A |
| 5927277 | Baudino et al. | Jul 1999 | A |
| 5941906 | Barreras et al. | Aug 1999 | A |
| 5957958 | Schulman et al. | Sep 1999 | A |
| 5975085 | Rise | Nov 1999 | A |
| 5978702 | Ward et al. | Nov 1999 | A |
| 5991668 | Leinders et al. | Nov 1999 | A |
| 6011996 | Gielen et al. | Jan 2000 | A |
| 6018682 | Rise | Jan 2000 | A |
| 6024095 | Stanley, III | Feb 2000 | A |
| 6033403 | Tu et al. | Mar 2000 | A |
| 6038480 | Hrdlicka et al. | Mar 2000 | A |
| 6050992 | Nichols | Apr 2000 | A |
| 6094598 | Elsberry et al. | Jul 2000 | A |
| 6104960 | Duysens et al. | Aug 2000 | A |
| 6109269 | Rise et al. | Aug 2000 | A |
| 6125300 | Weijand et al. | Sep 2000 | A |
| 6128537 | Rise | Oct 2000 | A |
| 6129685 | Howard, III | Oct 2000 | A |
| 6161047 | King et al. | Dec 2000 | A |
| 6205359 | Boveja | Mar 2001 | B1 |
| 6205361 | Kuzma et al. | Mar 2001 | B1 |
| 6216043 | Swanson et al. | Apr 2001 | B1 |
| 6227203 | Rise et al. | May 2001 | B1 |
| 6253109 | Gielen | Jun 2001 | B1 |
| 6253110 | Brabec et al. | Jun 2001 | B1 |
| 6263237 | Rise | Jul 2001 | B1 |
| 6266564 | Hill et al. | Jul 2001 | B1 |
| 6295476 | Schaenzer | Sep 2001 | B1 |
| 6319241 | King et al. | Nov 2001 | B1 |
| 6330466 | Hofmann et al. | Dec 2001 | B1 |
| 6337997 | Rise | Jan 2002 | B1 |
| 6343226 | Sunde et al. | Jan 2002 | B1 |
| 6353762 | Baudino et al. | Mar 2002 | B1 |
| 6356784 | Lozano et al. | Mar 2002 | B1 |
| 6356786 | Rezai et al. | Mar 2002 | B1 |
| 6356787 | Rezai et al. | Mar 2002 | B1 |
| 6364875 | Stanley, III | Apr 2002 | B1 |
| 6366813 | DiLorenzo | Apr 2002 | B1 |
| 6374140 | Rise | Apr 2002 | B1 |
| 6375666 | Mische | Apr 2002 | B1 |
| 6379353 | Nichols | Apr 2002 | B1 |
| 6415187 | Kuzma et al. | Jul 2002 | B1 |
| 6434431 | Camps et al. | Aug 2002 | B1 |
| 6479999 | DeMeester et al. | Nov 2002 | B1 |
| 6484059 | Gielen | Nov 2002 | B2 |
| 6493590 | Wessman et al. | Dec 2002 | B1 |
| 6529774 | Greene | Mar 2003 | B1 |
| 6538443 | Morich et al. | Mar 2003 | B2 |
| 6549812 | Smits | Apr 2003 | B1 |
| 6556873 | Smits | Apr 2003 | B1 |
| 6560472 | Hill et al. | May 2003 | B2 |
| 6560486 | Osorio et al. | May 2003 | B1 |
| 6587733 | Cross et al. | Jul 2003 | B1 |
| 6591128 | Wu et al. | Jul 2003 | B1 |
| 6594524 | Esteller et al. | Jul 2003 | B2 |
| 6597953 | Boling | Jul 2003 | B2 |
| 6643552 | Edell et al. | Nov 2003 | B2 |
| 6671544 | Baudino | Dec 2003 | B2 |
| 6675046 | Holsheimer | Jan 2004 | B2 |
| 6687538 | Hrdlicka et al. | Feb 2004 | B1 |
| 6690973 | Hill et al. | Feb 2004 | B2 |
| 6708064 | Rezai | Mar 2004 | B2 |
| 6718208 | Hill et al. | Apr 2004 | B2 |
| 6718211 | Smits | Apr 2004 | B2 |
| 6741893 | Smits | May 2004 | B2 |
| 6745079 | King | Jun 2004 | B2 |
| 6757970 | Kuzma et al. | Jul 2004 | B1 |
| 6795737 | Gielen et al. | Sep 2004 | B2 |
| 6804552 | Thompson et al. | Oct 2004 | B2 |
| 6818396 | Bloch et al. | Nov 2004 | B1 |
| 6829498 | Kipke et al. | Dec 2004 | B2 |
| 6850802 | Holsheimer | Feb 2005 | B2 |
| 6871098 | Nuttin et al. | Mar 2005 | B2 |
| 6882881 | Lesser et al. | Apr 2005 | B1 |
| 6892097 | Holsheimer | May 2005 | B2 |
| 6892438 | Hill et al. | May 2005 | B1 |
| 6904306 | Wu et al. | Jun 2005 | B1 |
| 6909920 | Lokhoff et al. | Jun 2005 | B2 |
| 6920359 | Meadows et al. | Jul 2005 | B2 |
| 6928320 | King | Aug 2005 | B2 |
| 6950706 | Rodriguez et al. | Sep 2005 | B2 |
| 6950709 | Baudino | Sep 2005 | B2 |
| 6978171 | Goetz et al. | Dec 2005 | B2 |
| 6978178 | Sommer et al. | Dec 2005 | B2 |
| 6999819 | Swoyer et al. | Feb 2006 | B2 |
| 7006859 | Osorio et al. | Feb 2006 | B1 |
| 7010351 | Firlik et al. | Mar 2006 | B2 |
| 7010356 | Jog et al. | Mar 2006 | B2 |
| 7024246 | Acosta et al. | Apr 2006 | B2 |
| 7035690 | Goetz | Apr 2006 | B2 |
| 7047082 | Schrom et al. | May 2006 | B1 |
| 7047084 | Erickson et al. | May 2006 | B2 |
| 7050856 | Stypulkowski | May 2006 | B2 |
| 7051419 | Schrom et al. | May 2006 | B2 |
| 7061240 | Ham et al. | Jun 2006 | B2 |
| 7063767 | Tyson et al. | Jun 2006 | B1 |
| 7076292 | Forsberg | Jul 2006 | B2 |
| 7077822 | Howard, III | Jul 2006 | B1 |
| 7107104 | Keravel et al. | Sep 2006 | B2 |
| 7133718 | Bakken et al. | Nov 2006 | B2 |
| 7146222 | Boling | Dec 2006 | B2 |
| 7151961 | Whitehurst et al. | Dec 2006 | B1 |
| 7174219 | Wahlstrand et al. | Feb 2007 | B2 |
| 7177701 | Pianca | Feb 2007 | B1 |
| 7181288 | Rezai et al. | Feb 2007 | B1 |
| 7184829 | Hill et al. | Feb 2007 | B2 |
| 7187978 | Malek et al. | Mar 2007 | B2 |
| 7191016 | Marshall et al. | Mar 2007 | B2 |
| 7191018 | Gielen et al. | Mar 2007 | B2 |
| 7200439 | Zdeblick et al. | Apr 2007 | B2 |
| 7203548 | Whitehurst et al. | Apr 2007 | B2 |
| 7204798 | Zdeblick et al. | Apr 2007 | B2 |
| 7204833 | Osorio et al. | Apr 2007 | B1 |
| 7209787 | Dilorenzo | Apr 2007 | B2 |
| 7212851 | Donoghue et al. | May 2007 | B2 |
| 7212867 | Van Venrooij et al. | May 2007 | B2 |
| 7214189 | Zdeblick | May 2007 | B2 |
| 7216000 | Sieracki et al. | May 2007 | B2 |
| 7216001 | Hacker et al. | May 2007 | B2 |
| 7231256 | Wahlstrand et al. | Jun 2007 | B2 |
| 7236822 | Dobak, III | Jun 2007 | B2 |
| 7242984 | DiLorenzo | Jul 2007 | B2 |
| 7276061 | Schaer et al. | Oct 2007 | B2 |
| 7280867 | Frei et al. | Oct 2007 | B2 |
| 7282030 | Frei et al. | Oct 2007 | B2 |
| 7282050 | Starkebaum et al. | Oct 2007 | B2 |
| 7286878 | Stypulkowski | Oct 2007 | B2 |
| 7286882 | Cole | Oct 2007 | B2 |
| 7288066 | Drew | Oct 2007 | B2 |
| 7289851 | Gunderson et al. | Oct 2007 | B2 |
| 7289852 | Helfinstine et al. | Oct 2007 | B2 |
| 7295880 | Gielen | Nov 2007 | B2 |
| 7298143 | Jaermann et al. | Nov 2007 | B2 |
| 7307223 | Tyson et al. | Dec 2007 | B2 |
| 7313430 | Urquhart et al. | Dec 2007 | B2 |
| 7313440 | Miesel | Dec 2007 | B2 |
| 7315759 | Markowitz et al. | Jan 2008 | B2 |
| 7317947 | Wahlstrand et al. | Jan 2008 | B2 |
| 7317948 | King et al. | Jan 2008 | B1 |
| 7319899 | Keizer | Jan 2008 | B2 |
| 7319904 | Cross et al. | Jan 2008 | B2 |
| 7321798 | Muhlenberg et al. | Jan 2008 | B2 |
| 7321837 | Osorio et al. | Jan 2008 | B2 |
| 7322832 | Kronich et al. | Jan 2008 | B2 |
| 7328057 | Freas et al. | Feb 2008 | B2 |
| 7328068 | Spinelli et al. | Feb 2008 | B2 |
| 7328069 | Gerber | Feb 2008 | B2 |
| 7330760 | Heruth et al. | Feb 2008 | B2 |
| 7337010 | Howard et al. | Feb 2008 | B2 |
| 7343206 | Sage et al. | Mar 2008 | B2 |
| 7346395 | Lozano et al. | Mar 2008 | B2 |
| 7356369 | Phillips et al. | Apr 2008 | B2 |
| 7359837 | Drew | Apr 2008 | B2 |
| 7366572 | Heruth et al. | Apr 2008 | B2 |
| 7367956 | King | May 2008 | B2 |
| 7369891 | Augustijn et al. | May 2008 | B2 |
| 7369893 | Gunderson | May 2008 | B2 |
| 7369894 | Gerber | May 2008 | B2 |
| 7385443 | Denison | Jun 2008 | B1 |
| 7388378 | Gray et al. | Jun 2008 | B2 |
| 7389147 | Wahlstrand et al. | Jun 2008 | B2 |
| 7390311 | Hildebrand et al. | Jun 2008 | B2 |
| 7391257 | Denison et al. | Jun 2008 | B1 |
| 7392089 | Wahlstrand et al. | Jun 2008 | B2 |
| 7395113 | Heruth et al. | Jul 2008 | B2 |
| 7400927 | Litvin | Jul 2008 | B1 |
| 7406351 | Wesselink | Jul 2008 | B2 |
| 7418292 | Shafer | Aug 2008 | B2 |
| 7421297 | Giftakis et al. | Sep 2008 | B2 |
| 7427280 | Gerber | Sep 2008 | B2 |
| 7429938 | Corndorf | Sep 2008 | B1 |
| 7433734 | King | Oct 2008 | B2 |
| 7442183 | Baudino et al. | Oct 2008 | B2 |
| 7447545 | Heruth et al. | Nov 2008 | B2 |
| 7450996 | MacDonald et al. | Nov 2008 | B2 |
| 7463917 | Martinez | Dec 2008 | B2 |
| 7463928 | Lee et al. | Dec 2008 | B2 |
| 7474247 | Heinks et al. | Jan 2009 | B1 |
| 7479910 | Heinks et al. | Jan 2009 | B1 |
| 7483748 | Torgerson et al. | Jan 2009 | B2 |
| 7489966 | Leinders et al. | Feb 2009 | B2 |
| 7489970 | Lee et al. | Feb 2009 | B2 |
| 7491181 | Heruth et al. | Feb 2009 | B2 |
| 7497844 | Spear et al. | Mar 2009 | B2 |
| 7497863 | Solar et al. | Mar 2009 | B2 |
| 7502217 | Zhao et al. | Mar 2009 | B2 |
| 7505815 | Lee et al. | Mar 2009 | B2 |
| 7505869 | Hartlaub | Mar 2009 | B2 |
| 7515961 | Germanson et al. | Apr 2009 | B2 |
| 7519431 | Goetz et al. | Apr 2009 | B2 |
| 7519432 | Bolea et al. | Apr 2009 | B2 |
| 7520890 | Phillips | Apr 2009 | B2 |
| 7526339 | Lahti et al. | Apr 2009 | B2 |
| 7526340 | Drew | Apr 2009 | B2 |
| 7526341 | Goetz et al. | Apr 2009 | B2 |
| 7529582 | DiLorenzo | May 2009 | B1 |
| 7529586 | Wahlstrand et al. | May 2009 | B2 |
| 7542803 | Heruth et al. | Jun 2009 | B2 |
| 7546164 | King | Jun 2009 | B2 |
| 7546166 | Michels et al. | Jun 2009 | B2 |
| 7548775 | Kipke et al. | Jun 2009 | B2 |
| 7548786 | Lee et al. | Jun 2009 | B2 |
| 7551951 | Osorio et al. | Jun 2009 | B1 |
| 7551960 | Forsberg et al. | Jun 2009 | B2 |
| 7555345 | Wahlstrand et al. | Jun 2009 | B2 |
| 7561921 | Phillips et al. | Jul 2009 | B2 |
| 7563141 | Alexander et al. | Jul 2009 | B2 |
| 7563541 | Howard et al. | Jul 2009 | B2 |
| 7578819 | Bleich et al. | Aug 2009 | B2 |
| 7580756 | Schulte et al. | Aug 2009 | B2 |
| 7582387 | Howard et al. | Sep 2009 | B2 |
| 7590451 | Tronnes et al. | Sep 2009 | B2 |
| 7590453 | Heruth et al. | Sep 2009 | B2 |
| 7590455 | Heruth et al. | Sep 2009 | B2 |
| 7591970 | Olson | Sep 2009 | B2 |
| 7594828 | Alexander et al. | Sep 2009 | B2 |
| 7594889 | St. Ores et al. | Sep 2009 | B2 |
| 7596399 | Singhal et al. | Sep 2009 | B2 |
| 7596408 | Singhal et al. | Sep 2009 | B2 |
| 7596415 | Brabec et al. | Sep 2009 | B2 |
| 7599730 | Hunter et al. | Oct 2009 | B2 |
| 7603161 | Wurmfeld et al. | Oct 2009 | B2 |
| 7603177 | Sieracki et al. | Oct 2009 | B2 |
| 7604629 | Gerber et al. | Oct 2009 | B2 |
| 7604644 | Schulte et al. | Oct 2009 | B2 |
| 7608458 | Soykan et al. | Oct 2009 | B2 |
| 7610083 | Drew et al. | Oct 2009 | B2 |
| 7611483 | Gerber et al. | Nov 2009 | B2 |
| 7614743 | Geiger | Nov 2009 | B2 |
| 7615015 | Coleman | Nov 2009 | B2 |
| 7616998 | Nuttin et al. | Nov 2009 | B2 |
| 7617002 | Goetz | Nov 2009 | B2 |
| 7620454 | Dinsmoor et al. | Nov 2009 | B2 |
| 7622303 | Soykan et al. | Nov 2009 | B2 |
| 7622988 | Denison et al. | Nov 2009 | B2 |
| 7623053 | Terry et al. | Nov 2009 | B2 |
| 7623918 | Goetz | Nov 2009 | B2 |
| 7623919 | Goetz et al. | Nov 2009 | B2 |
| 7623923 | Gerber et al. | Nov 2009 | B2 |
| 7623930 | Zeijlemaker et al. | Nov 2009 | B2 |
| 7624293 | Osorio et al. | Nov 2009 | B2 |
| 7628780 | Bonner et al. | Dec 2009 | B2 |
| 7631415 | Phillips et al. | Dec 2009 | B2 |
| 7632225 | Stypulkowski | Dec 2009 | B2 |
| 7635541 | Scott et al. | Dec 2009 | B2 |
| 7637867 | Zdeblick | Dec 2009 | B2 |
| 7640059 | Forsberg et al. | Dec 2009 | B2 |
| 7640060 | Zdeblick | Dec 2009 | B2 |
| 7641992 | Howard et al. | Jan 2010 | B2 |
| 7642013 | Howard et al. | Jan 2010 | B2 |
| 7647111 | Ries et al. | Jan 2010 | B2 |
| 7647116 | Bauhahn | Jan 2010 | B2 |
| 7647117 | Bauhahn | Jan 2010 | B2 |
| 7647121 | Wahlstrand et al. | Jan 2010 | B2 |
| 7650291 | Rosenfeld et al. | Jan 2010 | B2 |
| 7653433 | Lozano et al. | Jan 2010 | B2 |
| 7657318 | King et al. | Feb 2010 | B2 |
| 7657319 | Goetz et al. | Feb 2010 | B2 |
| 7660620 | Zeijlemaker et al. | Feb 2010 | B2 |
| 7660630 | Dudding et al. | Feb 2010 | B2 |
| 7662140 | Heruth et al. | Feb 2010 | B2 |
| 7662509 | Howard et al. | Feb 2010 | B2 |
| 7663066 | Tyson et al. | Feb 2010 | B2 |
| 7664551 | Cigaina | Feb 2010 | B2 |
| 7664552 | Wahlstrand et al. | Feb 2010 | B2 |
| 7668601 | Hegland et al. | Feb 2010 | B2 |
| 7671594 | Gray | Mar 2010 | B2 |
| 7676271 | Wahlstrand et al. | Mar 2010 | B2 |
| 7676273 | Goetz et al. | Mar 2010 | B2 |
| 7676274 | Hung et al. | Mar 2010 | B2 |
| 7680540 | Jensen et al. | Mar 2010 | B2 |
| 7682355 | Gerber et al. | Mar 2010 | B2 |
| 7682745 | Howard et al. | Mar 2010 | B2 |
| 7684860 | Wahlstrand et al. | Mar 2010 | B2 |
| 7684873 | Gerber | Mar 2010 | B2 |
| 7689289 | King | Mar 2010 | B2 |
| 7697972 | Verard et al. | Apr 2010 | B2 |
| 7697995 | Cross et al. | Apr 2010 | B2 |
| 7706124 | Zhao et al. | Apr 2010 | B2 |
| 7706889 | Gerber et al. | Apr 2010 | B2 |
| 7711421 | Shafer et al. | May 2010 | B2 |
| 7711428 | Janzig et al. | May 2010 | B2 |
| 7711436 | Stone | May 2010 | B2 |
| 7713194 | Zdeblick | May 2010 | B2 |
| 7713195 | Zdeblick | May 2010 | B2 |
| 7720548 | King | May 2010 | B2 |
| 7729768 | White et al. | Jun 2010 | B2 |
| 7729780 | Vardiman | Jun 2010 | B2 |
| 7738958 | Zdeblick et al. | Jun 2010 | B2 |
| 7742823 | King et al. | Jun 2010 | B2 |
| 7756588 | Jog et al. | Jul 2010 | B2 |
| 7797029 | Gibson et al. | Sep 2010 | B2 |
| 7822483 | Stone et al. | Oct 2010 | B2 |
| 7853303 | Nikumb et al. | Dec 2010 | B2 |
| 7877149 | Zdeblick | Jan 2011 | B2 |
| 7899539 | Whitehurst et al. | Mar 2011 | B2 |
| 7925329 | Zdeblick et al. | Apr 2011 | B2 |
| 7930035 | DiLorenzo | Apr 2011 | B2 |
| 7935056 | Zdeblick | May 2011 | B2 |
| 7941202 | Hetke et al. | May 2011 | B2 |
| 7945336 | Sauter-Starace et al. | May 2011 | B2 |
| 7969161 | Behzadi et al. | Jun 2011 | B2 |
| 7974705 | Zdeblick et al. | Jul 2011 | B2 |
| 7978064 | Zdeblick et al. | Jul 2011 | B2 |
| 7979105 | Kipke et al. | Jul 2011 | B2 |
| 7983751 | Zdeblick et al. | Jul 2011 | B2 |
| 8000794 | Lozano | Aug 2011 | B2 |
| 8000808 | Hegland et al. | Aug 2011 | B2 |
| 8032224 | Miesel et al. | Oct 2011 | B2 |
| 8036737 | Goetz et al. | Oct 2011 | B2 |
| 8036743 | Savage et al. | Oct 2011 | B2 |
| 8036748 | Zdeblick et al. | Oct 2011 | B2 |
| 8055334 | Savage et al. | Nov 2011 | B2 |
| 8055353 | Kreidler et al. | Nov 2011 | B2 |
| 8099170 | Jensen et al. | Jan 2012 | B2 |
| 8114021 | Robertson et al. | Feb 2012 | B2 |
| 8115618 | Robertson et al. | Feb 2012 | B2 |
| 8121687 | Jensen et al. | Feb 2012 | B2 |
| 8123684 | Zdeblick | Feb 2012 | B2 |
| 8172762 | Robertson | May 2012 | B2 |
| 8187161 | Li et al. | May 2012 | B2 |
| 8195308 | Frank et al. | Jun 2012 | B2 |
| 8204586 | Zdeblick | Jun 2012 | B2 |
| 8258962 | Robertson et al. | Sep 2012 | B2 |
| 8261428 | Fang et al. | Sep 2012 | B2 |
| 8280514 | Lozano et al. | Oct 2012 | B2 |
| 8332020 | Zdeblick | Dec 2012 | B2 |
| 8355768 | Masmanidis et al. | Jan 2013 | B2 |
| 8412347 | Zdeblick | Apr 2013 | B2 |
| 8473061 | Moffitt et al. | Jun 2013 | B2 |
| 8473069 | Bi et al. | Jun 2013 | B2 |
| 8489203 | Ortmann | Jul 2013 | B2 |
| 8788064 | Mercanzini et al. | Jul 2014 | B2 |
| 8874232 | Chen | Oct 2014 | B2 |
| 8897891 | Romero | Nov 2014 | B2 |
| 8938308 | Meadows | Jan 2015 | B2 |
| 20020062143 | Baudino et al. | May 2002 | A1 |
| 20030004553 | Grill et al. | Jan 2003 | A1 |
| 20030023282 | Barrett et al. | Jan 2003 | A1 |
| 20030036780 | Barrett et al. | Feb 2003 | A1 |
| 20030060822 | Schaer et al. | Mar 2003 | A1 |
| 20030083724 | Jog et al. | May 2003 | A1 |
| 20030100823 | Kipke et al. | May 2003 | A1 |
| 20030135253 | Kokones et al. | Jul 2003 | A1 |
| 20030176892 | Shalev | Sep 2003 | A1 |
| 20040002635 | Hargrove et al. | Jan 2004 | A1 |
| 20040015205 | Whitehurst et al. | Jan 2004 | A1 |
| 20040039434 | Schrom et al. | Feb 2004 | A1 |
| 20040102828 | Lowry et al. | May 2004 | A1 |
| 20040122335 | Sackellares et al. | Jun 2004 | A1 |
| 20040133390 | Osorio et al. | Jul 2004 | A1 |
| 20040138517 | Osorio et al. | Jul 2004 | A1 |
| 20040138536 | Frei et al. | Jul 2004 | A1 |
| 20040138720 | Naisberg et al. | Jul 2004 | A1 |
| 20040138722 | Carroll et al. | Jul 2004 | A1 |
| 20040152958 | Frei et al. | Aug 2004 | A1 |
| 20040172089 | Whitehurst et al. | Sep 2004 | A1 |
| 20040193021 | Zdeblick et al. | Sep 2004 | A1 |
| 20040215288 | Lee et al. | Oct 2004 | A1 |
| 20040220637 | Zdeblick et al. | Nov 2004 | A1 |
| 20040225335 | Whitehurst et al. | Nov 2004 | A1 |
| 20040243011 | Plaza | Dec 2004 | A1 |
| 20040249417 | Ransbury et al. | Dec 2004 | A1 |
| 20040254483 | Zdeblick et al. | Dec 2004 | A1 |
| 20050004627 | Gibson et al. | Jan 2005 | A1 |
| 20050008660 | Kipke et al. | Jan 2005 | A1 |
| 20050010261 | Luders et al. | Jan 2005 | A1 |
| 20050021103 | DiLorenzo | Jan 2005 | A1 |
| 20050027284 | Lozano et al. | Feb 2005 | A1 |
| 20050033136 | Govari et al. | Feb 2005 | A1 |
| 20050038489 | Grill | Feb 2005 | A1 |
| 20050049655 | Boveja et al. | Mar 2005 | A1 |
| 20050070971 | Fowler et al. | Mar 2005 | A1 |
| 20050075681 | Rezai et al. | Apr 2005 | A1 |
| 20050113882 | Cameron et al. | May 2005 | A1 |
| 20050137647 | Wallace et al. | Jun 2005 | A1 |
| 20050143790 | Kipke et al. | Jun 2005 | A1 |
| 20050154425 | Boveja et al. | Jul 2005 | A1 |
| 20050171558 | Abovitz et al. | Aug 2005 | A1 |
| 20050182455 | Thrope et al. | Aug 2005 | A1 |
| 20050209511 | Heruth et al. | Sep 2005 | A1 |
| 20050209513 | Heruth et al. | Sep 2005 | A1 |
| 20050209643 | Heruth et al. | Sep 2005 | A1 |
| 20050222642 | Przybyszewski et al. | Oct 2005 | A1 |
| 20050240242 | DiLorenzo | Oct 2005 | A1 |
| 20050245988 | Miesel | Nov 2005 | A1 |
| 20060004422 | De Ridder | Jan 2006 | A1 |
| 20060030897 | Gilmer et al. | Feb 2006 | A1 |
| 20060041295 | Osypka | Feb 2006 | A1 |
| 20060049957 | Surgenor et al. | Mar 2006 | A1 |
| 20060058588 | Zdeblick | Mar 2006 | A1 |
| 20060058727 | Bernabei | Mar 2006 | A1 |
| 20060058855 | Gill | Mar 2006 | A1 |
| 20060095105 | Jog et al. | May 2006 | A1 |
| 20060116581 | Zdeblick et al. | Jun 2006 | A1 |
| 20060129203 | Garabedian et al. | Jun 2006 | A1 |
| 20060135877 | Giftakis et al. | Jun 2006 | A1 |
| 20060149336 | Meadows | Jul 2006 | A1 |
| 20060149337 | John | Jul 2006 | A1 |
| 20060167497 | Armstrong et al. | Jul 2006 | A1 |
| 20060173263 | He et al. | Aug 2006 | A1 |
| 20060173510 | Besio et al. | Aug 2006 | A1 |
| 20060178709 | Foster et al. | Aug 2006 | A1 |
| 20060195154 | Jaax et al. | Aug 2006 | A1 |
| 20060200206 | Firlik et al. | Sep 2006 | A1 |
| 20060212090 | Lozano et al. | Sep 2006 | A1 |
| 20060241717 | Whitehurst et al. | Oct 2006 | A1 |
| 20060258951 | Bleich et al. | Nov 2006 | A1 |
| 20060264777 | Drew | Nov 2006 | A1 |
| 20060276866 | McCreery | Dec 2006 | A1 |
| 20060282014 | Kipke et al. | Dec 2006 | A1 |
| 20060293720 | Dilorenzo | Dec 2006 | A1 |
| 20060293721 | Tarver et al. | Dec 2006 | A1 |
| 20070027498 | Maschino et al. | Feb 2007 | A1 |
| 20070027500 | Maschino et al. | Feb 2007 | A1 |
| 20070027514 | Gerber | Feb 2007 | A1 |
| 20070043268 | Russell | Feb 2007 | A1 |
| 20070060974 | Lozano | Mar 2007 | A1 |
| 20070067002 | Lozano | Mar 2007 | A1 |
| 20070067003 | Sanchez et al. | Mar 2007 | A1 |
| 20070088403 | Wyler et al. | Apr 2007 | A1 |
| 20070088404 | Wyler et al. | Apr 2007 | A1 |
| 20070093870 | Maschino | Apr 2007 | A1 |
| 20070100389 | Jaax et al. | May 2007 | A1 |
| 20070100392 | Maschino et al. | May 2007 | A1 |
| 20070100393 | Whitehurst et al. | May 2007 | A1 |
| 20070100398 | Sloan | May 2007 | A1 |
| 20070106143 | Flaherty | May 2007 | A1 |
| 20070123765 | Hetke et al. | May 2007 | A1 |
| 20070123944 | Zdeblick | May 2007 | A1 |
| 20070135721 | Zdeblick | Jun 2007 | A1 |
| 20070142872 | Mickle et al. | Jun 2007 | A1 |
| 20070150024 | Leyde et al. | Jun 2007 | A1 |
| 20070173890 | Armstrong | Jul 2007 | A1 |
| 20070173896 | Zdeblick | Jul 2007 | A1 |
| 20070173897 | Zdeblick | Jul 2007 | A1 |
| 20070173901 | Reeve | Jul 2007 | A1 |
| 20070173908 | Begnaud | Jul 2007 | A1 |
| 20070179558 | Gliner et al. | Aug 2007 | A1 |
| 20070179569 | Zdeblick | Aug 2007 | A1 |
| 20070185537 | Zdeblick | Aug 2007 | A1 |
| 20070185544 | Dawant et al. | Aug 2007 | A1 |
| 20070185548 | Zdeblick | Aug 2007 | A1 |
| 20070185549 | Zdeblick | Aug 2007 | A1 |
| 20070197892 | Shen et al. | Aug 2007 | A1 |
| 20070203537 | Goetz et al. | Aug 2007 | A1 |
| 20070203546 | Stone et al. | Aug 2007 | A1 |
| 20070208394 | King et al. | Sep 2007 | A1 |
| 20070213784 | Pless | Sep 2007 | A1 |
| 20070213785 | Osorio et al. | Sep 2007 | A1 |
| 20070213786 | Sackellares et al. | Sep 2007 | A1 |
| 20070219591 | Zdeblick et al. | Sep 2007 | A1 |
| 20070225674 | Molnar et al. | Sep 2007 | A1 |
| 20070225773 | Shen et al. | Sep 2007 | A1 |
| 20070225774 | Eskandar et al. | Sep 2007 | A1 |
| 20070233192 | Craig | Oct 2007 | A1 |
| 20070249953 | Frei et al. | Oct 2007 | A1 |
| 20070249954 | Virag et al. | Oct 2007 | A1 |
| 20070250133 | Carlson et al. | Oct 2007 | A1 |
| 20070255323 | Werder et al. | Nov 2007 | A1 |
| 20070255338 | Wahlstrand | Nov 2007 | A1 |
| 20070255374 | Kolafa et al. | Nov 2007 | A1 |
| 20070255531 | Drew | Nov 2007 | A1 |
| 20070265683 | Ehrlich | Nov 2007 | A1 |
| 20070282389 | Moxon et al. | Dec 2007 | A1 |
| 20070293908 | Cowan et al. | Dec 2007 | A1 |
| 20080021514 | Pless | Jan 2008 | A1 |
| 20080021517 | Dietrich | Jan 2008 | A1 |
| 20080027289 | Zdeblick | Jan 2008 | A1 |
| 20080027487 | Patel et al. | Jan 2008 | A1 |
| 20080027503 | Marrosu et al. | Jan 2008 | A1 |
| 20080027504 | Bedenbaugh | Jan 2008 | A1 |
| 20080027540 | Cumming | Jan 2008 | A1 |
| 20080039895 | Fowler et al. | Feb 2008 | A1 |
| 20080046012 | Covalin et al. | Feb 2008 | A1 |
| 20080046013 | Lozano | Feb 2008 | A1 |
| 20080058630 | Robertson | Mar 2008 | A1 |
| 20080077186 | Thompson et al. | Mar 2008 | A1 |
| 20080077191 | Morrell | Mar 2008 | A1 |
| 20080103547 | Okun et al. | May 2008 | A1 |
| 20080103548 | Fowler et al. | May 2008 | A1 |
| 20080103578 | Gerber | May 2008 | A1 |
| 20080114417 | Leyde | May 2008 | A1 |
| 20080119900 | DiLorenzo | May 2008 | A1 |
| 20080139870 | Gliner et al. | Jun 2008 | A1 |
| 20080140152 | Imran et al. | Jun 2008 | A1 |
| 20080154328 | Thompson et al. | Jun 2008 | A1 |
| 20080154331 | John et al. | Jun 2008 | A1 |
| 20080161881 | Firlik et al. | Jul 2008 | A1 |
| 20080161896 | Sauter-Starace et al. | Jul 2008 | A1 |
| 20080172103 | Kao et al. | Jul 2008 | A1 |
| 20080177196 | Burdick et al. | Jul 2008 | A1 |
| 20080188905 | Swartz | Aug 2008 | A1 |
| 20080195166 | Sun et al. | Aug 2008 | A1 |
| 20080195227 | Boling et al. | Aug 2008 | A1 |
| 20080208283 | Vetter et al. | Aug 2008 | A1 |
| 20080208287 | Palermo et al. | Aug 2008 | A1 |
| 20080215125 | Farah et al. | Sep 2008 | A1 |
| 20080221642 | Humayun et al. | Sep 2008 | A1 |
| 20080242976 | Robertson et al. | Oct 2008 | A1 |
| 20080255439 | Tang et al. | Oct 2008 | A1 |
| 20080255629 | Jenson et al. | Oct 2008 | A1 |
| 20080255647 | Jensen et al. | Oct 2008 | A1 |
| 20080269835 | Carlson et al. | Oct 2008 | A1 |
| 20080269842 | Giftakis et al. | Oct 2008 | A1 |
| 20080275526 | Lozano | Nov 2008 | A1 |
| 20080284599 | Zdeblick et al. | Nov 2008 | A1 |
| 20080294218 | Savage et al. | Nov 2008 | A1 |
| 20080300652 | Lim et al. | Dec 2008 | A1 |
| 20080306394 | Zdeblick et al. | Dec 2008 | A1 |
| 20080312726 | Frank et al. | Dec 2008 | A1 |
| 20080316020 | Robertson et al. | Dec 2008 | A1 |
| 20090027504 | Lim et al. | Jan 2009 | A1 |
| 20090062879 | Li et al. | Mar 2009 | A1 |
| 20090082645 | Hafezi et al. | Mar 2009 | A1 |
| 20090105784 | Massoud-Ansari et al. | Apr 2009 | A1 |
| 20090118806 | Vetter et al. | May 2009 | A1 |
| 20090132042 | Hetke et al. | May 2009 | A1 |
| 20090171416 | Firlik et al. | Jul 2009 | A1 |
| 20090177144 | Masmanidis et al. | Jul 2009 | A1 |
| 20090187196 | Vetter | Jul 2009 | A1 |
| 20090204183 | Kreidler et al. | Aug 2009 | A1 |
| 20090240314 | Kong et al. | Sep 2009 | A1 |
| 20090253977 | Kipke et al. | Oct 2009 | A1 |
| 20090256702 | Robertson et al. | Oct 2009 | A1 |
| 20090292325 | Cederna et al. | Nov 2009 | A1 |
| 20090299174 | Wright et al. | Dec 2009 | A1 |
| 20090306728 | Wright et al. | Dec 2009 | A1 |
| 20090306729 | Doerr | Dec 2009 | A1 |
| 20090312770 | Kozai et al. | Dec 2009 | A1 |
| 20090318824 | Nishida et al. | Dec 2009 | A1 |
| 20090325424 | Aarts et al. | Dec 2009 | A1 |
| 20100014541 | Harriman | Jan 2010 | A1 |
| 20100015274 | Fill | Jan 2010 | A1 |
| 20100030298 | Martens et al. | Feb 2010 | A1 |
| 20100036468 | Decre et al. | Feb 2010 | A1 |
| 20100069717 | Hafezi et al. | Mar 2010 | A1 |
| 20100076536 | Merz et al. | Mar 2010 | A1 |
| 20100087853 | Kipke et al. | Apr 2010 | A1 |
| 20100100152 | Martens et al. | Apr 2010 | A1 |
| 20100106178 | Obermiller et al. | Apr 2010 | A1 |
| 20100114193 | Lozano et al. | May 2010 | A1 |
| 20100114234 | Zdeblick | May 2010 | A1 |
| 20100114250 | Zdeblick | May 2010 | A1 |
| 20100130844 | Williams et al. | May 2010 | A1 |
| 20100145216 | He et al. | Jun 2010 | A1 |
| 20100145414 | Decre et al. | Jun 2010 | A1 |
| 20100152747 | Padiy et al. | Jun 2010 | A1 |
| 20100198315 | Martens et al. | Aug 2010 | A1 |
| 20100249883 | Zdeblick | Sep 2010 | A1 |
| 20100274305 | Gliner et al. | Oct 2010 | A1 |
| 20100292602 | Worrell et al. | Nov 2010 | A1 |
| 20100298908 | Vardiman | Nov 2010 | A1 |
| 20100298917 | Vardiman | Nov 2010 | A1 |
| 20100298918 | Vardiman | Nov 2010 | A1 |
| 20100312188 | Robertson et al. | Dec 2010 | A1 |
| 20100312228 | Zdeblick et al. | Dec 2010 | A1 |
| 20100318163 | Zdeblick | Dec 2010 | A1 |
| 20100331807 | Whitehurst et al. | Dec 2010 | A1 |
| 20110001488 | Behzadi et al. | Jan 2011 | A1 |
| 20110022124 | Zdeblick et al. | Jan 2011 | A1 |
| 20110034964 | Bi et al. | Feb 2011 | A1 |
| 20110034970 | Barker | Feb 2011 | A1 |
| 20110040203 | Savage et al. | Feb 2011 | A1 |
| 20110071766 | Dolan et al. | Mar 2011 | A1 |
| 20110130809 | Zdeblick | Jun 2011 | A1 |
| 20110152988 | Whitehurst et al. | Jun 2011 | A1 |
| 20110154655 | Hetke et al. | Jun 2011 | A1 |
| 20110184495 | Wang et al. | Jul 2011 | A1 |
| 20110190860 | Harberts et al. | Aug 2011 | A1 |
| 20110196454 | Strand et al. | Aug 2011 | A1 |
| 20110208225 | Martens et al. | Aug 2011 | A1 |
| 20110213382 | Decre et al. | Sep 2011 | A1 |
| 20110218417 | Boogaard et al. | Sep 2011 | A1 |
| 20110224757 | Zdeblick et al. | Sep 2011 | A1 |
| 20110224765 | Harberts et al. | Sep 2011 | A1 |
| 20110224766 | Tol et al. | Sep 2011 | A1 |
| 20110282179 | Zdeblick | Nov 2011 | A1 |
| 20120004520 | Whitworth et al. | Jan 2012 | A1 |
| 20120004527 | Thompson et al. | Jan 2012 | A1 |
| 20120004716 | Langhammer et al. | Jan 2012 | A1 |
| 20120007734 | Berkman et al. | Jan 2012 | A1 |
| 20120022341 | Zdeblick | Jan 2012 | A1 |
| 20120035684 | Thompson et al. | Feb 2012 | A1 |
| 20120053344 | Lagos Gonzalez | Mar 2012 | A1 |
| 20120059444 | Pardoel et al. | Mar 2012 | A1 |
| 20120062379 | Hafezi et al. | Mar 2012 | A1 |
| 20120095355 | Zdeblick | Apr 2012 | A1 |
| 20120109262 | Martens | May 2012 | A1 |
| 20120109599 | Martens | May 2012 | A1 |
| 20120116188 | Frank et al. | May 2012 | A1 |
| 20120136420 | Pardoel et al. | May 2012 | A1 |
| 20120150256 | Martens | Jun 2012 | A1 |
| 20120184837 | Martens et al. | Jul 2012 | A1 |
| 20120253442 | Gliner et al. | Oct 2012 | A1 |
| 20120277821 | Martens et al. | Nov 2012 | A1 |
| 20120296444 | Greenberg et al. | Nov 2012 | A1 |
| 20120303088 | Van Kaam et al. | Nov 2012 | A1 |
| 20120303089 | Martens et al. | Nov 2012 | A1 |
| 20120303107 | Decre et al. | Nov 2012 | A1 |
| 20120316630 | Firlik et al. | Dec 2012 | A1 |
| 20130009691 | Blanken et al. | Jan 2013 | A1 |
| 20130030366 | Robertson et al. | Jan 2013 | A1 |
| 20130046356 | Jensen et al. | Feb 2013 | A1 |
| 20130060102 | Zdeblick | Mar 2013 | A1 |
| 20130085361 | Mercanzini et al. | Apr 2013 | A1 |
| 20130131754 | Sarvazyan | May 2013 | A1 |
| 20130144132 | Hafezi et al. | Jun 2013 | A1 |
| 20130172716 | Lozano et al. | Jul 2013 | A1 |
| 20130193950 | Hafezi et al. | Aug 2013 | A1 |
| 20130204318 | Young | Aug 2013 | A1 |
| 20130223028 | Arne et al. | Aug 2013 | A1 |
| 20130231188 | Berberich et al. | Sep 2013 | A1 |
| 20130282090 | Decre et al. | Oct 2013 | A1 |
| 20130345780 | Tabada et al. | Dec 2013 | A1 |
| 20130345789 | Havel et al. | Dec 2013 | A1 |
| 20140039578 | Whitehurst et al. | Feb 2014 | A1 |
| Number | Date | Country |
|---|---|---|
| 0 677 743 | Oct 1995 | EP |
| 0 743 839 | Nov 1996 | EP |
| 0 892 654 | Jan 1999 | EP |
| 0 895 483 | Feb 1999 | EP |
| 0 959 942 | Dec 1999 | EP |
| 1 048 319 | Nov 2000 | EP |
| 1 062 973 | Dec 2000 | EP |
| 1 102 607 | May 2001 | EP |
| 1 257 320 | Nov 2002 | EP |
| 1 446 189 | Aug 2004 | EP |
| 1 514 576 | Mar 2005 | EP |
| 1 750 798 | Feb 2007 | EP |
| 1 890 764 | Feb 2008 | EP |
| 1 931 419 | Jun 2008 | EP |
| 1 985 579 | Oct 2008 | EP |
| 1 993 665 | Nov 2008 | EP |
| 2 046 441 | Apr 2009 | EP |
| 2 066 396 | Jun 2009 | EP |
| 2 069 003 | Jun 2009 | EP |
| 2 131 916 | Dec 2009 | EP |
| 2 167 188 | Mar 2010 | EP |
| 2 320 221 | May 2011 | EP |
| 2 341 979 | Jul 2011 | EP |
| 2 456 513 | May 2012 | EP |
| 2 542 303 | Jan 2013 | EP |
| 2 559 454 | Feb 2013 | EP |
| 2 604 313 | Jun 2013 | EP |
| 2 620 179 | Jul 2013 | EP |
| 2 623 154 | Aug 2013 | EP |
| 2 626 108 | Aug 2013 | EP |
| 2 626 109 | Aug 2013 | EP |
| 2 626 110 | Aug 2013 | EP |
| 2 626 111 | Aug 2013 | EP |
| 2 656 875 | Oct 2013 | EP |
| 2 656 876 | Oct 2013 | EP |
| 2 674 193 | Dec 2013 | EP |
| WO-9810010 | Mar 1998 | WO |
| WO-03022354 | Mar 2003 | WO |
| WO-03028521 | Apr 2003 | WO |
| WO-03066152 | Aug 2003 | WO |
| WO 03066153 | Aug 2003 | WO |
| WO-03066157 | Aug 2003 | WO |
| WO-2004045707 | Jun 2004 | WO |
| WO-2005002467 | Jan 2005 | WO |
| WO-2005067792 | Jul 2005 | WO |
| WO-2005112216 | Nov 2005 | WO |
| WO-2006104432 | Oct 2006 | WO |
| WO-2007002144 | Jan 2007 | WO |
| WO-2007009070 | Jan 2007 | WO |
| WO-2007011611 | Jan 2007 | WO |
| WO-2007025356 | Mar 2007 | WO |
| WO-2007028003 | Mar 2007 | WO |
| WO-2007042999 | Apr 2007 | WO |
| WO-2007092330 | Aug 2007 | WO |
| WO-2007100428 | Sep 2007 | WO |
| WO-2007108718 | Sep 2007 | WO |
| WO-2008003318 | Jan 2008 | WO |
| WO-2008005478 | Jan 2008 | WO |
| WO-2008016881 | Feb 2008 | WO |
| WO-2008035285 | Mar 2008 | WO |
| WO-2008035344 | Mar 2008 | WO |
| WO-2008051463 | May 2008 | WO |
| WO-2008064269 | May 2008 | WO |
| WO-2008068759 | Jun 2008 | WO |
| WO-2008075294 | Jun 2008 | WO |
| WO-2008077440 | Jul 2008 | WO |
| WO-2008089726 | Jul 2008 | WO |
| WO-2008107822 | Sep 2008 | WO |
| WO-2008109298 | Sep 2008 | WO |
| WO-2008133616 | Nov 2008 | WO |
| WO-2008133683 | Nov 2008 | WO |
| WO-2008138305 | Nov 2008 | WO |
| WO-2010014686 | Feb 2010 | WO |
| WO-2010055421 | May 2010 | WO |
| WO-2011115999 | Sep 2011 | WO |
| WO-2013014206 | Jan 2013 | WO |
| Entry |
|---|
| US 8,388,533, 03/2013, Hafezi et al. (withdrawn) |
| US 8,469,885, 06/2013, Hafezi et al. (withdrawn) |
| Rousche, et al., “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Transactions on Biomedical Engineering 48(3): 361-371 (Mar. 2001). |
| Sepulveda et al., “Finite Element Analysis of Current Pathways with Implanted Electrodes”, J. Biomed. Eng. 1983, vol. 5, pp. 41-48. |
| International Search Report for PCT/EP2011/055045 dated Jul. 18, 2011 (4 pages). |
| U.S. Appl. No. 07/151,961, filed Feb. 3, 1988, Masahiko Okunuki et al. |
| Australian Patent Examination Report No. 1 dated Jan. 30, 2014 in corresponding Australian Application No. 2010326613, 2 pages. |
| Australian Patent Examination Report No. 1 dated Jan. 31, 2014 in corresponding Australian Application No. 2009315316, 3 pages. |
| Benabid, et al. “Combined (Thalamotomy and Stimulation) Stereotactic Surgery of the VIM Thalamic Nucleus for Bilateral Parkinson Disease”, Proceedings of the Meeting of the American Society for Stereotactic and Functional Neurosurgery, Montreal 1987 Appl. Neurophysiol. 50: 344-346. |
| Canadian Office Action for Application No. 2,743,575 dated Sep. 25, 2014, 3 pages. |
| Cogan, Stuart F., et al. “Plasma-enhanced chemical vapor deposited silicon carbide as an implantable dielectric coating.” Journal of Biomedical Materials Research Part A 67.3 (2003): 856-867. |
| Communication from the European Patent Office in Application No. 09795810.2 dated Sep. 14, 2011. |
| Decision of Rejection and Decision for Dismissal of Amendment in JP Patent Application No. 2011-543841 dated May 15, 2014. |
| EIC Biomedical, “Thin-film Encapsulation for Neural Recording and Stimulation Electrodes”, Silicon carbide and oxycarbide, Apr. 2008: pp. 1-2. |
| English translation of Notice of Reasons for Rejection in JP application No. 2011-543841 dated Oct. 21, 2013. |
| European Communication and Search Report for Application No. 09795810.2 dated Sep. 25, 2013. |
| European Communication mailed May 22, 2013 including search report for EP application No. 12198290.4-1652. |
| European Search Report for Appl. Ser. No. 09803534.8 dated Jul. 21, 2011. |
| European Search Report for Appl. Ser. No. 13169272.5 dated Aug. 30, 2013. |
| European Search Report for application No. EP 14172592 dated Aug. 28, 2014, 8 pages. |
| Examination Report for EP09795810.2 dated Jun. 22, 2012. |
| Examination Report from European Patent Office in 09 795 810.2 dated May 8, 2014. |
| Examination Report in AU Patent Application No. 2009276603 dated Mar. 3, 2014. |
| Fierce Medical Devices, “Medtronic Announces First U.S. Implant of World's Smallest, Minimally Invasive Cardiac Pacemaker”, Feb. 20, 2014, pp. 1-3. |
| Gibney, “St. Jude places its Nanostim leadless pacemaker in a U.K. patient”, Fierce Medical Devices, Jan. 27, 2014, pp. 1-3. |
| International Preliminary Report on Patentability for PCT/EP2010/068658 dated Jun. 5, 2012. |
| International Preliminary Report on Patentability for PCT/IB2009/007715 dated May 17, 2011. |
| International Preliminary Report on Patentability for PCT/US2009/052077 dated Feb. 1, 2011. |
| International Search Report and Written Opinion for PCT/EP2010/068658 dated Mar. 21, 2011. |
| International Search Report and Written Opinion in PCT/US09/52077 dated Sep. 25, 2009. |
| International Search Report for PCT/IB2009/007715 dated Apr. 22, 2010. |
| Notice of Allowance for U.S. Appl. No. 14/287,917 dated Apr. 15, 2015. |
| Notice of Reasons for Rejection for Japanese Patent Application No. 2011-543841 dated May 30, 2013. |
| Notice of Reasons for Rejection in JP Patent Application No. 2011-521276 dated Mar. 3, 2014. |
| Notice of Reasons for Rejection in JP Patent Application No. 2011-521276 dated May 30, 2013. |
| Notice of Reasons for Rejections for Japanese Patent Appl. Ser. No. 2012-541491 dated Aug. 28, 2014, 8 pages. |
| Office Action for Canadian Appl. Ser. No. 2743575 dated Jan. 21, 2015 (4 pages). |
| Office Action for EPO Appl. Ser. No. 10787404.2 dated May 6, 2015. |
| Office Action for European Application No. 10787404.2 dated Mar. 26, 2013. |
| Office Action for Japanese Appl. Ser. No. 2013-501857 dated Jun. 1, 2015. |
| Office Action for Japanese Appl. Ser. No. 2013-501857 dated Sep. 17, 2014. |
| Pollak, et al. “Effets de la Stimulation du Noyau Sous-Thalamique Dans La Maladie De Parkinson”, Rev. Neurol (Paris),149, 3, 175-176. Mason, Paris, 1993. |
| Second Notice of Reasons for Rejection for Japanese Application No. 2012-541491 mailed Apr. 8, 2015. |
| US Notice of Allowance for U.S. Appl. No. 14/316,154 dated Apr. 20, 2015. |
| US Notice of Allowance for U.S. Appl. No. 13/512,936 dated Feb. 20, 2014. |
| US Notice of Allowance for U.S. Appl. No. 13/512,936 dated Nov. 25, 2013. |
| US Notice of Allowance for U.S. Appl. No. 13/056,261 dated May 8, 2014. |
| US Notice of Allowance in U.S. Appl. No. 13/128,821 dated Dec. 24, 2013. |
| US Notice of Allowance in U.S. Appl. No. 13/128,821 dated Mar. 25, 2014. |
| US Office Action for U.S. Appl. No. 13/128,821 dated Dec. 14, 2012. |
| US Office Action for U.S. Appl. No. 13/128,821 dated Apr. 24, 2012. |
| US Office Action for U.S. Appl. No. 14/316,154 dated Dec. 18, 2014. |
| US Office Action for U.S. Appl. No. 13/512,936 dated Aug. 14, 2013. |
| US Office Action for U.S. Appl. No. 13/056261 dated Jan. 9, 2014. |
| US Office Action in U.S. Appl. No. 13/056,261 dated Aug. 7, 2013. |
| US Office Action on U.S. Appl. No. 14/287,917 dated Sep. 26, 2014. |
| Written Opinion for PCT/EP2010/068658 dated Jun. 1, 2012. |
| Written Opinion for Singapore Application No. 201103393-3 dated May 2, 2012. |
| Written Opinion of the International Search Authority for PCT/IB2009/07715 dated May 12, 2011. |
| Office Action for Canadian Appl. Ser. No. 2732309 dated Dec. 7, 2015. |
| US Notice of Allowance for U.S. Appl. No. 14/470,356 dated Apr. 13, 2016. |
| US Notice of Allowance for U.S. Appl. No. 14/470,356 dated Mar. 18, 2016. |
| US Office Action for U.S. Appl. No. 14/309,491 dated Mar. 3, 2016. |
| US Office Action for U.S. Appl. No. 14/470,423 dated Jan. 21, 2016. |
| US Office Action for U.S. Appl. No. 13/128,821 dated Nov. 14, 2013. |
| US Corrected Notice of Allowability for U.S. Appl. No. 14/470,356 dated May 18, 2016. |
| US Notice of Allowance for U.S. Appl. No. 14/309,491 dated May 11, 2016. |
| Decision of Rejection for Japanese Appl. Ser. No. 2012-541491 dated Oct. 26, 2015. |
| International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/IB2015/053610 dated Jul. 20, 2015. |
| International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/IB2015/056437 dated Nov. 5, 2015. |
| International Search Report and Written Opinion for PCT Ser. Appl. No. PCT/IB2015/056438 dated Nov. 5, 2015. |
| Office Action for Canadian Appl. Ser. No. 2743575 dated Jun. 11, 2015. |
| Office Action for Canadian Appl. Ser. No. 2743575 dated Sep. 14, 2015. |
| Office Action for EPO Appl. Ser. No. 14172592.9 dated Aug. 20, 2015. |
| US Notice of Allowance for U.S. Appl. No. 14/287,917 dated Jul. 20, 2015. |
| US Office Action for U.S. Appl. No. 14/309,491 dated Jul. 28, 2015. |
| Number | Date | Country | |
|---|---|---|---|
| 20130085361 A1 | Apr 2013 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61320089 | Apr 2010 | US |
