US 10,293,164 B2Grant
Apparatus and methods for assisted breathing by transvascular nerve stimulation
Issue Date:2019-05-21
•22 Claims
•13 Drawing Sheets
Abstract
A catheter may include an outer layer defining a plurality of apertures therethrough, and a body defining at least one longitudinal lumen therein. The body may be within the outer layer, and the apertures may be radially outward of the lumen. The catheter may also include a plurality of electrodes positioned in or on the catheter, with each electrode being electrically exposed through an aperture of the plurality of apertures. A ribbon cable may extend through the lumen and include a plurality of leads, with the plurality of leads being electrically connected to the plurality of electrodes. The plurality of leads and electrodes may be formed by the deposition of conductive inks or paints, or by the electrodeposition of copper or other conductive metals or materials.
Metadata
Assignee
- Lungpacer Medical Inc.
Inventors
- John E. Nash
- Douglas G. Evans
- Viral Thakkar
Application Information
Application Number:US 15/606,867
Filing Date:2017-05-26
Priority Date:2017-05-26
Art Unit:3792
Classifications
IPC:
A61N1/36A61N1/05
Patent Drawings (13 sheets)
Description
Technical Field
[0001] Embodiments of this disclosure relate to medical apparatus and particularly to apparatus applicable for the restoration, enhancement, or modulation of physiological functions. Specific embodiments provide apparatus for stimulating the phrenic nerves to contract the diaphragm muscle to assist breathing by transvascular electrical stimulation of nerves.
Background
[0002] Electrical stimulation of nerves is widely applied in the treatment of a range of conditions and may be applied to control muscle activity or to generate sensations. Muscles and nerves may be stimulated by placing electrodes in, around, or near the muscles and nerves and by activating the electrodes by means of an implanted or external source of energy (e.g. electricity).
[0003] The diaphragm muscle provides important functions for respiration. The phrenic nerves normally transmit signals from the brain to cause the contractions of the diaphragm muscle necessary for breathing. However, various conditions can prevent appropriate signals from being delivered to the phrenic nerves. These include:
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- [0004] permanent or temporary injury or disease affecting the spinal cord or brain stem;
- [0005] Amyotrophic Lateral Sclerosis (ALS);
- [0006] decreased day or night ventilatory drive (e.g. central sleep apnea, Ondine's curse); and
- [0007] decreased ventilatory drive while under the influence of anesthetic agents and/or mechanical ventilation.
These conditions affect a significant number of people.
[0008] Intubation and positive pressure mechanical ventilation (MV) may be used for periods of several hours or several days, sometimes weeks, to help critically ill patients breathe while in intensive care units (ICU). Some patients may be unable to regain voluntary breathing and thus require prolonged or permanent mechanical ventilation. Although mechanical ventilation can be initially lifesaving, it has a range of significant problems and/or side effects. Mechanical ventilation:
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- [0009] often causes ventilator-induced lung injury (VILI) and alveolar damage which can lead to accumulation of fluid in the lungs and increased susceptibility to infection (ventilator-associated pneumonia; VAP);
- [0010] commonly requires sedation to reduce discomfort and anxiety in acutely intubated patients;
- [0011] leads to rapid atrophy of the disused diaphragm muscle (ventilator-induced diaphragm dysfunction, VIDD);
- [0012] can adversely affect venous return because the lungs are pressurized and the diaphragm is inactive;
- [0013] interferes with eating and speaking;
- [0014] requires apparatus that is not readily portable; and
- [0015] increases the risk of dying if the patient fails to regain normal breathing and becomes ventilator-dependent.
[0016] A patient who is sedated and connected to a mechanical ventilator cannot breathe normally because the central neural drive to the diaphragm and accessory respiratory muscles is suppressed. Inactivity leads to muscle disuse atrophy and an overall decline in well-being. Diaphragm muscle atrophy occurs rapidly and can be a serious problem to the patient. According to a published study in organ donor patients (Levine et al., New England Journal of Medicine, 358: 1327-1335, 2008) after only 18 to 69 hours of mechanical ventilation, all diaphragm muscle fibers had shrunk on average by 52-57%. Muscle fiber atrophy results in muscle weakness and increased fatigability. Therefore, ventilator-induced diaphragm atrophy could cause a patient to become ventilator-dependent. It has been estimated that over 600,000 US patients will be ventilator dependent and require prolonged mechanical ventilation by the year 2020 (Zilberberg et al., Critical Care Medicine, 36(5): 1451-1455, 2008).
[0017] It may also be necessary during MV to deliver or remove one or more fluids or to obtain sensor readings from within the patient. Smaller patients, such as, for example, neonates, may require smaller medical instruments to perform the aforementioned procedures. Additionally, as with any medical procedure, the risk of injury to the patient increases with the length and complexity of the medical procedure.
[0018] There remains a need for cost-effective, practical, surgically simple and minimally invasive apparatus and methods that may be applied to stimulate breathing, deliver treatment, and perform tests. There is also a need for apparatus and methods for facilitating patients on MV to regain the capacity to breathe naturally and to be weaned from MV.
Summary
[0019] Embodiments of the present disclosure relate to, among other things, medical apparatus and methods for nerve stimulation. Specific embodiments provide apparatus for stimulating breathing by trans-vascular electrical stimulation of nerves. Each of the embodiments disclosed herein may include one or more of the features described in connection with any of the other disclosed embodiments.
[0020] In one embodiment, a catheter may include an outer layer defining a plurality of apertures therethrough, and a body defining at least one longitudinal lumen therein. The body may be within the outer layer, and the apertures may be radially outward of the lumen. A plurality of electrodes may be positioned in or on the catheter, and each electrode may be electrically exposed through an aperture of the plurality of apertures, or alternatively mounted on the surface of the catheter. A ribbon cable may extend through the lumen and include a plurality of leads. The plurality of leads may electrically connect to the plurality of electrodes.
[0021] The catheter may further include one or more of the following features. The lumen may be a groove or recessed channel exposed along a portion of the circumference of the body along at least a portion of the length of the body, and the groove may be at least partially covered by an outer layer. The plurality of leads may be at least partially surrounded by a non-conducting material. The ribbon cable may include a plurality of corrugations. The catheter may also include at least one filler positioned within at least a portion of the corrugations. The corrugations may be positioned radially inward of at least one electrode. The catheter may also include at least one fluid lumen and a guide wire lumen.
[0022] Further, the catheter may include a connector feed and an application specific integrated circuit (“ASIC”) radially inward of the outer layer. The ASIC may connect the connector feed to the ribbon cable. The ribbon cable may include several, for example three, branches of ribbon cable, and the at least one longitudinal lumen may include three longitudinal lumens spaced circumferentially around an exterior of the body and radially inward of the outer layer. In this example, the three branches may extend distally from the ASIC, and each of the three branches may connect to at least one electrode through a corresponding longitudinal lumen. One branch of the three branches may include at least one lead that electrically connects at least one proximal electrode and at least one other lead that electrically connects at least one distal electrode. The plurality of apertures may include a plurality of proximal apertures and a plurality of distal apertures. The proximal apertures may include two longitudinally extending rows, and the distal apertures may include two longitudinally extending rows. One row of proximal apertures may be circumferentially aligned with one row of distal apertures. The ribbon cable may be electrically connected to at least one electrode via a connection and an electrode coupler, and the electrode coupler may longitudinally overlap with the ribbon cable and be positioned radially inward of a portion of the electrode.
[0023] In another alternative or additional embodiment, the catheter may include an outer layer defining a plurality of apertures therethrough, and a body radially within the outer layer. The catheter may also include a radial extension, extending helically around and radially outward from the body and within the outer layer, as well as a ribbon cable coupled to a plurality of electrodes. The ribbon cable may extend around an exterior of the body between portions of the radial extension, with each electrode of the plurality of electrodes electrically exposed through an aperture of the plurality of apertures, the apertures in this case being formed in an outer insulating layer over the electrodes.
[0024] The catheter may further include one or more of the following features. The plurality of electrodes may be coupled to the ribbon cable at approximately a 45 degree angle relative to a longitudinal axis of the ribbon cable. The catheter may include at least one ASIC positioned radially inward of the outer layer, and the at least one ASIC may electrically connect the ribbon cable to at least one of the plurality of electrodes. The body may include at least one groove exposed along a circumference of the body along at least a portion of the length of the body, and the at least one ASIC may be positioned within the at least one groove. The catheter may include at least one ASIC for each of the plurality of electrodes, and each ASIC may electrically connect the ribbon cable to the corresponding electrode. The catheter may include a conductive liner positioned over or within the apertures.
[0025] In another alternative or additional embodiment, the catheter may include an outer layer or sleeve. The outer layer may include first and second longitudinally extending rows of distal apertures in the outer layer, and the outer layer and/or the catheter may also include a first radiopaque feature for confirming an orientation of the first row of distal apertures relative to the second row of distal apertures.
[0026] The catheter may further include one or more of the following features. The catheter may further include first and second longitudinally extending rows of proximal apertures in the outer layer. The outer layer may include a second radiopaque feature for confirming an orientation of the first row of proximal apertures relative to the second row of proximal apertures. The first row of proximal apertures may be circumferentially aligned with one of either the first row of distal apertures or the second row of distal apertures. The second row of proximal apertures may be circumferentially offset from both the first row of distal apertures and the second row of distal apertures. The second radiopaque feature may include a radiopaque marker positioned circumferentially opposite to a line extending between the first and second rows of proximal apertures. The first radiopaque feature may be at a distal portion of the outer layer, and the second radiopaque feature may be at a proximal portion of the outer layer. The catheter may further include a hub, and the hub may include an orientation feature. The hub may also include a port configured to couple the hub to a proximal portion of the catheter in a particular orientation.
[0027] Further aspects of the disclosures and features of example embodiments are illustrated in the appended drawings and/or described in the text of this specification and/or described in the accompanying claims. It may be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. As used herein, the terms “comprises,” “comprising,” or other variations thereof, are intended to cover a non-exclusive inclusion such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such a process, method, article, or apparatus. Additionally, the term “exemplary” is used herein in the sense of “example,” rather than “ideal.” As used herein, the terms “about,” “substantially,” and “approximately,” indicate a range of values within +/−5% of a stated value.
Brief Description of the Drawings
[0028] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate non-limiting embodiments of the present disclosure and together with the description serve to explain the principles of the disclosure.
[0029] FIG. 1 illustrates the anatomy of selected nerves and blood vessels in a person's neck and upper torso, along with an exemplary catheter and control unit.
[0030] FIG. 2 illustrates a ventral view of an exemplary catheter having windows that align with nerve-stimulating electrodes within the catheter, inserted in a person's neck and upper torso, according to an exemplary embodiment.
[0031] FIG. 3 illustrates a perspective view of a catheter with conductors and electrodes printed on the exterior of the catheter, according to an exemplary embodiment.
[0032] FIG. 4 illustrates a perspective view of a tubular member with conductors, an application specific integrated circuit, and electrodes, where the tubular member may be an internal part of a catheter, according to an exemplary embodiment.
[0033] FIG. 5 illustrates a schematic view of the conductors, application specific integrated circuit, and electrodes of the exemplary embodiment shown in FIG. 4 .
[0034] FIG. 6 illustrates a cross-sectional view of a catheter with an exemplary tubular member including conductors, electrodes, and lumens, according to an exemplary embodiment.
[0035] FIG. 7A illustrates an exemplary embodiment of a conductor and electrode assembly of a catheter, and FIG. 7B illustrates an exploded view of another exemplary embodiment of a conductor and electrode assembly.
[0036] FIG. 8 illustrates a perspective view of a portion of a tubular member with axial lumens and a radial extension, according to an exemplary embodiment.
[0037] FIG. 9 illustrates a portion of a conductive ribbon cable with electrodes that may be coupled around the tubular member of FIG. 8 within the radial extension, according to an exemplary embodiment.
[0038] FIG. 10 illustrates a cross-sectional view of a catheter with the exemplary tubular member of FIG. 8 and the ribbon cable with electrodes of FIG. 9 , according to an exemplary embodiment.
[0039] FIG. 11 illustrates a cross-sectional view of a catheter with an exemplary tubular member similar to FIG. 6 with a plurality of application specific integrated circuits.
[0040] FIG. 12 illustrates the anatomy of selected nerves and blood vessels in a person's neck and upper torso along with an exemplary catheter and control unit connected via a wireless connection, according to an exemplary embodiment.
[0041] FIG. 13 illustrates an exemplary catheter with radiopaque electrodes, according to an exemplary embodiment.
[0042] FIG. 14 illustrates an exemplary catheter with radiopaque electrodes and orientation-aiding indicators, according to an exemplary embodiment.
Detailed Description
[0043] Throughout the following description, specific details are set forth to provide a more thorough understanding to persons skilled in the art. The following description of examples of the technology is not intended to be exhaustive or to limit the system to the precise forms of any example embodiment. Accordingly, the description and drawings are to be regarded in an illustrative, rather than a restrictive, sense.
[0044] Reference will now be made in detail to examples of the present disclosure described above and illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
[0045] The terms “proximal” and “distal” are used herein to refer to the relative positions of the components of an exemplary medical device or insertion device. When used herein, “proximal” refers to a position relatively closer to the exterior of the body or closer to an operator using the medical device or insertion device. In contrast, “distal” refers to a position relatively further away from the operator using the medical device or insertion device, or closer to the interior of the body.
[0046] General Overview
[0047] In general, embodiments of this disclosure relate to medical devices and methods for electrically stimulating a patient's nerves. In one embodiment, the patient's nerves may be stimulated to activate the diaphragm to restore or control breathing.
[0048] The medical devices described herein may include several components, including a catheter having a tubular member and one or more electrode assemblies, a signal generator to provide stimulation energy to the electrode assemblies, and one or more sensors to sense the condition of the patient and adjust the stimulation signals. The medical devices may further include a steering mechanism. Various embodiments of catheters are disclosed, including windowed catheters, multi-lumen catheters, and radiopaque catheters. In addition, various embodiments of electrode assemblies are disclosed, which may be used alone, in combination with other electrode assemblies, and with any of the disclosed tubular members that form the outer portion of the catheters.
[0049] The different embodiments of the various medical device components (e.g., electrode assemblies, steering mechanisms, etc.) may be combined and used together in any logical arrangement. Furthermore, individual features or elements of any described embodiment may be combined with or used in connection with the individual features or elements of other embodiments. The various embodiments may further be used in different contexts than those specifically described herein. For example, the disclosed electrode structures may be combined or used in combination with various deployment systems known in the art for various diagnostic and/or therapeutic applications.
[0050] During use, the medical devices (e.g., a catheter with one or more electrode assemblies) may be inserted into a patient's blood vessels such that the electrode assemblies are near the patient's nerves. The electrode assemblies may then be used for transvascular electrical stimulation of the patient's nerves. The disclosed devices may be optimized for rapid, temporary deployment in a patient and easy removal from the patient. The disclosed devices may be used, for example, for restoring breathing, treating conditions such as disuse muscle atrophy and chronic pain, or for any other procedures involving nerve stimulation. The disclosed devices may be used to treat acute or chronic conditions.
Medical Device Overview: Catheter and Electrode Assemblies
[0051] FIG. 1 illustrates a medical system 10 that includes a catheter 12 including a plurality of lumens and having two proximal electrode assemblies 14 and two distal electrode assemblies 16. The electrode assemblies 14 and 16 may be positioned on or within a tubular member or catheter body of catheter 12. Catheter 12 may be positioned within a patient through the patient's external or internal jugular veins 18, brachiocephalic veins 20, superior vena cava 22, brachial vein (not shown), radial vein (not shown), and/or left subclavian vein 24 such that the proximal electrode assemblies 14 are directed towards the left phrenic nerve 26, and the distal electrode assemblies 16 are directed laterally towards the right phrenic nerve 28. As such, when positioned, catheter 12 may receive signals from a control unit 30 and, using electrode assemblies 14 and 16, stimulate the left phrenic nerve 26 and/or the right phrenic nerve 28.
[0052] Catheter 12 may further include a manifold 32 that extends external to the patient. Electrical cable 34 and pigtail lumen 36 extend from manifold 32. Cable 34 and pigtail lumen 36 may include cable connectors 38 and 40 to connect external elements, and cable 34 may be coupled to electrical control unit 30 via cable connector 38. The cables 34 and 36 may be formed of electrical leads (not shown) that connect to electrode assemblies 14 and 16. Cable connectors 38 and 40 may be attached (e.g. by solder, crimp, PCB, etc.) to the cables 34 and 36, and one or both of cable connectors 38 and 40 may include a threading 41 (as shown in FIGS. 2 and 3 ). Alternatively or additionally, one or both of cable connectors 38 and 40 may include a push-to-pull compression fitting or a slip-lock fitting (not shown). Control unit 30 and other elements may be electronically connected to the components within catheter 12 to both send and receive signals and/or data to selectively stimulate electrode assemblies 14, 16 and/or monitor the patient and any response to the stimulation. Alternatively or additionally, cables 34 and 36 may include one or more lumens or fluid lines that connect to one or more internal lumens in catheter 12, and cable connectors 38 and 40 may form sealed connections with a fluid port or other source. Catheter 12 may also include an atraumatic distal tip 42.
[0053] As shown in FIG. 2 , catheter 12 may include two axially extending rows of proximal apertures or windows 44. Each axially extending row includes proximal windows 44 positioned at the same circumferential position around the exterior of catheter 12, but at different axial positions along the exterior of catheter 12. The two rows of proximal windows 44 may be substantially aligned. For instance, as illustrated in FIG. 2 , one proximal window 44 of a first row is located at the same axial position as a window of a second row, but at a different circumferential position around the exterior of the catheter 12. When positioned in a patient, the two rows of proximal windows 44 may be substantially posterior facing, and at least one proximal window 44 may face, abut or be positioned in the vicinity of the left phrenic nerve 26.
[0054] Catheter 12 may also include two axially extending rows of distal apertures or windows 46. Again, each axially extending row includes distal windows 46 positioned at the same circumferential position around the exterior of catheter 12, but at different axial positions along the exterior of catheter 12. The two rows of distal windows 46 may be unaligned such that one distal window 46 of a first row is axially between two distal windows 46 of a second row. For instance, as illustrated in FIG. 2 , one distal window 46 of a first row is located at a different axial position and at a different circumferential position around the exterior of the catheter 12 than a window of the second row. When positioned in a patient, the two rows of distal windows 46 may be substantially laterally facing (to the patient's right), and at least one distal window 46 may face, abut, or be positioned in the vicinity of the right phrenic nerve 28. Therefore, in the example shown in FIG. 2 , when viewed ventrally, the two unaligned rows of three distal windows 46 may appear as one row of six distal windows 46, because one row is anterior facing (shown as dark windows) and one row is posterior facing (shown as lighter windows).
[0055] The proximal windows 44 and the distal windows 46 may be positioned on catheter 12 such that one row of proximal windows 44 is circumferentially aligned (i.e., the same circumferential position but different axial position) with one row of distal windows 46, but another row of proximal windows 44 and another row of distal windows 46 are each circumferentially offset from the aligned rows on the catheter 12. Proximal electrode assemblies 14 may include individual proximal electrodes 48 that are positioned to be aligned with (e.g., radially inward of and underneath) proximal windows 44, and distal electrode assemblies 16 may include individual distal electrodes 50 that are positioned to be aligned with (e.g., radially inward of and underneath) distal windows 46. Windows 44, 46 may expose electrodes 48, 50, allowing for a conductive path between sets or pairs of electrodes 48, 50 and surrounding tissue, including the blood vessel lumen in which catheter 12 is inserted.
[0056] In one embodiment illustrated in FIG. 2 , catheter 12 includes twelve proximal windows 44 (two rows of six windows 44) and six distal windows 46 (two rows of three windows 46). However, in other embodiments, the catheter 12 may include fewer or more rows and numbers of proximal or distal windows 46. For example, in other embodiments, the catheter 12 may include two, four, eight, ten, twelve, or more proximal windows 44 arranged in one, two, three, or more rows, and/or two, four, six, eight, ten, twelve or more distal windows 46 arranged in one, two, three, or more rows. The proximal windows 44 and distal windows 46 may be configured in pairs such that the catheter 12 has an even number of proximal windows 44 and an even number of distal windows 46. However, the number of windows 44 or 46 may also be an odd number.
[0057] The windows 44, 46 may be cut (e.g. by a laser, manual skive, drill, punch, etc.) through the exterior wall of catheter 12, or the windows 44, 46 may be formed by any other suitable method, such as during an extrusion process. 3-D printing, or other manufacturing process. The windows 44, 46 may extend along the longitudinal axis of catheter 12, or they may have a rectangular, oval, square, or any other shape. The windows 44, 46 may be apertures configured to allow electrical signals to travel from an interior lumen of the catheter 12 to the exterior of the catheter 12. In an additional or alternative embodiment, the windows 44, 46 may be covered by a material that allows electrical signals to pass through. As can be seen in the figures, the proximal windows 44 may be rotationally offset from the distal windows 46. In other words, in one embodiment, a straight line drawn proximally through a row of distal windows 46 does not necessarily pass through a row of proximal windows 44. In other embodiments, one or more rows of proximal windows 44 may be aligned with a corresponding row of distal windows 46. Furthermore, the characteristics of the proximal windows 44 may differ from the characteristics of the distal windows 46.
[0058] The dimensions of catheter 12 may be customized in accordance with the anatomy of a particular patient (e.g., different sizes of humans, pigs, chimpanzees, etc.). However, in some embodiments, the length of the section of the catheter 12 that includes the proximal windows 44 may be 10 cm or less, between 3-5 cm, or between 1-3 cm. The distance between two adjacent proximal windows 44 (whether the windows are circumferentially adjacent or longitudinally adjacent on the same row of windows) may be 5 cm or less, 3 cm or less, may be around 1 cm, or may be less than 1 cm. The length of the section of the catheter 12 that includes the distal windows 46 may be 6 cm or less, between 2-4 cm, or between 1-2 cm. The distance between two adjacent distal windows 46 (whether circumferentially adjacent or longitudinally adjacent on the same row of windows) may be 5 cm or less, 3 cm or less, may be around 1 cm, or may be less than 1 cm. The length of the section of the catheter 12 between proximal windows 44 and distal windows 46, which may be free of windows, may be 12 cm or less, 10 cm or less, or 8 cm or less. The windows 44, 46 may have a length of 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less, 2 mm or less, or 1 mm or less. In one embodiment, the windows 44, 46 may have a length that is less than the length of corresponding electrodes that are electrically exposed through the windows. These catheter dimensions are exemplary only, and the catheter 12 may have dimensions that vary from the above ranges and specific measurements. For neonatal applications, the distance between the distal electrodes and the proximal electrodes may be very small, perhaps less than 1 cm or even less than 1 mm. Alternatively, in this situation, a signal electrode array may contain electrode combinations which suitably serve to stimulate both the left phrenic nerve and the right phrenic nerve.
[0059] Additionally, catheter 12 may include windows 44, 46 in different configurations than discussed above. For example, catheter 12 may include more than two longitudinally extending rows of proximal windows 44 positioned at different circumferential positions. As such, catheter 12 may provide for more than two proximal electrode assemblies 14, or for two proximal electrode assemblies 14 to be positioned in different configurations in catheter 12. Alternatively or additionally, catheter 12 may be rotatable about the longitudinal axis such that windows 44, 46 at various circumferential positions may be positioned in different positions relative to the targeted nerves. Varying configurations may provide for various stimulation patterns with which catheter 12 may stimulate targeted nerves.
[0060] In one embodiment, medical system 10 may be assembled by positioning proximal and distal electrode assemblies 14, 16 within the outer, windowed tubular member of catheter 12 such that proximal electrodes 48 are at least partially exposed through proximal windows 44 and distal electrodes 50 are at least partially exposed through distal windows 46. The proximal electrode assemblies 14 may include the proximal electrodes 48 arranged and oriented to most effectively stimulate a nerve extending at transverse or right angles to the catheter 12 (e.g., the left phrenic nerve 26 in FIGS. 1 and 2 ), and the distal electrode assemblies 16 may include the distal electrodes 50 arranged and oriented to most effectively stimulate a nerve extending approximately parallel to the catheter 12 (e.g., the right phrenic nerve 28 in FIGS. 1 and 2 ). In an additional or alternative embodiment, the proximal electrode assemblies 14 may include proximal electrodes 48 arranged and oriented to most effectively stimulate a nerve extending approximately parallel to the catheter 12, and the distal electrode assemblies 16 may include distal electrodes 50 arranged and oriented to most effectively stimulate a nerve extending at transverse or right angles to the catheter 12. In the embodiments described above, the distal electrode assemblies 16 have been placed in a more distal location along catheter 12 than the proximal electrode assemblies 14. However, in other embodiments, the electrode assemblies 14, 16 may be rearranged within the catheter 12, and the proximal windows 44 and distal windows 46 of the catheter 12 may be configured to accommodate the alternative placement of the electrode assemblies 14, 16.
[0061] Distal tip 42 may be a tapered distal end portion of catheter 12. Distal tip 42 may be open at the distal end to allow a guide wire 52 to pass through and distally beyond catheter 12. Distal tip 42 may have a smaller circumference than the body of catheter 12. Distal tip 42 may be softer than other portions of catheter 12, be atraumatic, and have rounded edges. Distal tip 42 may be made of an aliphatic polyester-based thermoplastic polyurethane with a portion, for example, of 20% barium sulfate. Distal tip 42 may be formed and/or coupled to a remainder of catheter 12 by melting an extruded tube of thermoplastic polyurethane in a mold using, for example, an induction heater.
[0062] The medical system 10 may be used to rhythmically activate the diaphragm by inserting the catheter 12, with one or more electrode assemblies 14 and 16, percutaneously into central veins of a patient, as shown by FIG. 1 . Guide wire 52 may be used to position catheter 12 within a patient. For example, the Seldinger technique may be used, in which guide wire 52 is inserted through a hypodermic needle into a vein. As in the example shown in FIGS. 1 and 2 , the catheter 12 may be inserted into the left subclavian vein 24 and advanced into the superior vena cava 22. In an unillustrated example, catheter 12 may be inserted into the left jugular vein and advanced into the superior vena cava 22. In either example, catheter 12 may be inserted in a minimally-invasive way and may be temporarily placed into, and thus removable from, the patient. The distal tip 42 of the catheter 12 may then be passed over the guide wire 52 and advanced into the vein. The shape and mechanical properties of the catheter 12 may be designed to urge the catheter 12 to gently hug the vein wall in regions adjacent to the right and left phrenic nerves, as shown in FIG. 1 . The guide wire 52 may also be positioned such that it is adjacent to the right and left phrenic nerves before the distal tip of the catheter 12 is passed over the guide wire 52. When the catheter 12 is positioned, the guide wire 52 may extend distal to the catheter 12 from distal tip 42, through an internal lumen in catheter 12, through pigtail lumen 36, and proximally out of a cable connector 40, as shown in FIG. 2 .
[0063] Once the catheter 12 is fully inserted into the patient, various electrodes or electrode combinations can be tested to locate nerves of interest and to determine which electrodes most effectively stimulate the nerves of interest. For example, in one embodiment, testing may be done to locate the right phrenic nerve 28 and to determine which group of distal electrodes 50 in the distal electrode assemblies 16 most effectively stimulate the right phrenic nerve 28. Similarly, testing may be done to locate the left phrenic nerve 26 and to determine which group of proximal electrodes 48 in the proximal electrode assemblies 14 most effectively stimulate the left phrenic nerve 26. This testing and nerve location may be controlled and/or monitored via control unit 30, which may include testing programming and/or applications. For example, control unit 30 may test the electrodes and electrode combinations to determine which pair of bipolar distal electrodes 50 most effectively stimulate the right phrenic nerve 28, and which pair of bipolar proximal electrodes 48 most effectively stimulate the left phrenic nerve 26. Alternatively, control unit 30 may test the electrodes or electrode combinations to determine which tripolar or multipolar electrode combinations most effectively stimulate the phrenic nerves (for example, one cathode electrode and two anode electrodes, two cathode electrodes and one anode electrode, one cathode electrode and three anode electrodes, three cathode electrodes and one anode electrode, two cathode electrodes and two anode electrodes, one cathode electrode and four anode electrodes, four cathode electrodes and one anode electrode, one cathode electrode and five anode electrodes, five cathode electrodes and one anode electrode, etc.).
[0064] As a non-limiting example, testing could involve the use of a signal generator to systematically send electrical impulses to selected electrodes. By observing the patient's condition or by using sensors (either within or separate from the catheter 12), the ideal stimulation electrodes may be identified. Electrodes may serve as both stimulating electrodes and as sensing electrodes, and the medical system 10 may be integrated into a mechanical ventilator, which can be used to sense the patient's condition. Moreover, for example, control unit 30 may be programmed and/or activated to (a) select a first stimulation group of electrodes from the proximal electrode assemblies 14 to stimulate the left phrenic nerve 26, (b) select a second stimulation group of electrodes from the distal electrode assemblies 16 to stimulate the right phrenic nerve 28, (c) select a first stimulation current for the first stimulation group of electrodes to stimulate the left phrenic nerve 26, and (d) select a second stimulation current for the second stimulation group of electrodes to stimulate the right phrenic nerve 28. The selection of electrodes and current level may be pre-programmed or input based on the patient's characteristics, or the control unit 30 may test different electrode groups and current levels and monitor the patient's response to determine the electrode pairs and current levels. For example, the monitoring of the patient's response may include manual palpitation of the thoracic region, sensors to sense the movement of the patient's chest wall (e.g., accelerometers, optical devices, camera based sensors, etc.), airflow sensors, airway pressure sensors, central venous pressure sensors, etc. Control unit 30 may include a stimulation signal generator to generate the stimulation signals and to selectively transmit the generated signals to the selected electrodes.
[0065] Once ideal electrode combinations (e.g. pair, triplets, etc.) have been identified, an electrical potential may be created between a pair of selected bipolar electrodes, for example, a pair of proximal electrodes 48 each aligning with a proximal window 44. The arrangement of the electrodes 48 and the windows 44 may create an electrical field in the vicinity of windows 44, and thus in the vicinity of the targeted nerve, for example, the left phrenic nerve 26. During nerve stimulation, however, electrical current flows from one or more of the electrodes 48 to one or more of the other of the electrodes 48, flowing through the windows 44 and through the blood and surrounding tissues. The catheter 12 with windows 44 therefore acts as an insulating barrier that constrains and focuses the electrical field, rather than allowing the electrical field to expand radially outwards in all directions as the electrical field might with ring electrodes. The focused electrical field allows target nerve stimulation at lower, and thus safer, energy levels and avoids stimulating unwanted nerves or other structures. In some embodiments, the stimulation current may be between 10 and 6000 nC (nano-coulombs) or between 50-500 nC, reducing the risk of overstimulation or unwanted activation of nearby structures such as other nerves, muscles, or the heart.
[0066] In a further embodiment, any of the proximal electrodes 48 or the distal electrodes 50 may be used to measure electrical signals or other data from within the patient's body. In other words, in addition or alternatively to emitting or receiving electrical energy to produce a localized current for nerve stimulation, the electrodes 48, 50 may serve as sensors that receive electrical signals or other types of information from the patient.
Printed Ink Catheter
[0067] FIG. 3 illustrates an exemplary catheter 12A with electrode assemblies 14A, 16A and leads 54A printed directly onto the exterior of catheter 12A. Proximal electrode assemblies 14A, distal electrode assemblies 16A, and leads 54A may be formed by conductive inks (such as silver flakes or carbon flakes suspended in polymer or graphene ink). The conductive inks may be deposited and adhered directly onto the catheter 12A and sealed with an outer polyurethane or other flexible, insulating film or sheath, leaving the electrodes 48A, 50A of the electrode assemblies 14A, 16A at least partially exposed. The insulating film or sheath may be applied to the conductive inks that form electrode assemblies 14A, 16A and leads 54A, or may be applied to the catheter 12A as a whole. In some instances, the insulating film or sheath may be applied by 3-D printing or by other manufacturing processes. For example, at least one tubular sleeve (not shown) may be slid over at least a portion the exterior of catheter 12A. The tubular sleeve may be formed by extrusion, and/or the sleeve may be formed of a thin, thermoplastic material such as, but not limited to, polyamide, polyether block amide, polyurethane, silicone rubber, nylon, polyethylene, fluorinated hydrocarbon polymers, etc. Examples of polymer materials suitable for use in the sleeve are commercially available under the trademarks PEBAX™ and PELLETHANE™. The sleeve may be thermally bonded or mechanically attached to catheter 12A.
[0068] The exposed electrodes 48A, 50A may be coated with a conductive material (e.g., titanium nitride) in order to, for example, provide corrosion resistance and reduce the likelihood of silver oxide formation, which may be toxic. The conductive leads 54A electrically connect the proximal electrode assemblies 14A and the distal electrode assemblies 16A through cable 34 to control unit 30 or other electronics. The leads 54A connected to distal electrode assemblies 16A may travel proximally along catheter 12A beyond the proximal electrode assemblies 14A, for example, on the back side of catheter 12A in FIG. 3 .
[0069] As shown in FIG. 3 , proximal electrode assemblies 14A and distal electrode assemblies 16A may extend partially circumferentially around a portion of catheter 12A, and, for example, may be partially helical around a portion of the exterior of catheter 12A. Proximal electrode assemblies 14A and distal electrode assemblies 16A may be approximately 90 degrees displaced about a circumference of catheter 12A. For example, as shown in FIG. 3 , proximal electrode assemblies 14A may extend helically 180 degrees around the front portion of the catheter 12A, and distal electrode assemblies 16A may extend helically 180 degrees around the top (plane of the paper) portion of the catheter 12A, and the proximal electrode assemblies 14A and distal electrode assemblies 16A are approximately 90 degrees displaced at right angles to the plane of the paper. As such, the partially helical electrodes 48A, 50A may increase the conductive surface area and broaden the electrical field produced by the electrodes 48A, 50A while still focusing the field on a portion of the circumference of the catheter 12A positioned proximate to, abutting, or facing the target nerve.
[0070] The use of printed electrodes and leads may reduce the overall complexity of the design while maximizing the useable catheter lumen space, without drastically changing the catheter profile or flexibility. The use of printed electrodes 14A, 16A and printed leads 54A also allows freedom of electrode position and electrode shape, permitting optimization of field focus and minimum energy for nerve recruitment and capture. Printed leads 54A may be helically disposed between printed electrodes 14A, 16A to allow for greater flexibility in bending the catheter 12A. Additionally, in some embodiments, the profile of the catheter 12A may be reduced because of the space saved by using electrodes printed on the exterior of the catheter 12A, for example, for use with neonate or other young patients. In an additional or alternative embodiment, one or several catheter lumens may be used for fluid delivery, blood sampling, central venous pressure monitoring, or to accommodate tools, sensors, or other objects. In another additional or alternative embodiment, several of the catheter lumens may be eliminated, allowing for larger catheter lumens and/or reducing the cross-sectional size of the catheter 12A.
Catheters Including Ribbon Cables
[0071] Referring now to FIGS. 4-6 , a catheter body or tubular member 56 may form the interior of the catheter 12. As shown, tubular member 56 may include a guide wire lumen 58, at least two fluid lumens 60 and 62, and three lumens or grooves 64, 66, and 68. As discussed, guide wire 52 may be threaded though guide wire lumen 58. The fluid lumens 60 and 62 may be used to deliver and/or remove fluids at a treatment site. Additionally or alternatively, fluid lumens 60 and/or 62 may be used for other medical devices to treat, diagnose, or sense conditions at the surgical site. Grooves 64, 66, and 68 may, for example, be approximately rectangular in a cross-section. Grooves 64, 66, and 68 may extend radially to the outer surface of tubular member 56 and longitudinally along the tubular member 56. Grooves 64, 66, and 68 are exposed along at least a circumference and a portion of a length of tubular member 56 and may be spaced approximately 90 degrees from each other around the circumference of the tubular member 56. Grooves 64, 66, and 68 in tubular member 56 may accommodate electrical leads to connect control unit 30 to proximal electrodes 48 (shown in FIGS. 4 and 6 ) and distal electrodes 50. As shown, electrodes 48, 50 may extend longitudinally over a portion of tubular member 56 and may approximate the width of the grooves 64, 66, and 68 and/or the width of windows 44, 46.
[0072] In one aspect, the leads may be formed by ribbon cables 70′, 70″, and 70′″. As shown in FIG. 4 , a connector feed 72 may be positioned within groove 66 and recessed within the outer perimeter of tubular member 56. Connector feed 72 may send and transmit signals to an application specific integrated circuit (“ASIC”) 74. Connector feed 72 may also be formed by a ribbon cable. ASIC 74 may then be connected to three ribbon cables 70′, 70″, and 70′″ that branch out and connect to the proximal electrode assemblies 14 and distal electrode assemblies 16. Ribbon cables 70′, 70″, and 70′″ may be accommodated in grooves 64, 66, and 68 in tubular member 56. Partially circumferential grooves 69 extend around at least part of a circumference of the tubular member 56 to allow the ribbon cables 70′, 70″, and 70′″ to branch out without extending away from or interfering with the tubular member 56 fitting within an outer covering of catheter 12.
[0073] Ribbon cables 70′, 70″, and 70′″ are flexible and include multiple insulated leads 76 (some of which are labeled in FIG. 6 ) connected along their lengths to form a single, flexible planar structure. The planar structure is flexible to allow the formation of other shapes, such as bends and/or corrugations. The leads 76 within ribbon cables 70′, 70″, and 70′″ may include a wire or a rod-like conductive member. Leads 76 are surrounded by a layer of non-conducting material 78, such as insulation (FIG. 6 ). Ribbon cables 70′, 70″, and 70′″ may be similar to printed circuits formed using thin flexible polyimide substrates with copper plated conductors. Typical dimensions include an insulation base layer about 0.0381 mm (0.0015 in) thick, a copper conductor about 0.0381 mm (0.0015 in) thick by 0.0508 mm (0.002 in) wide, an insulation cover layer about 0.0381 mm (0.0015 in) thick, and a lateral spacing between conductors of about 0.0381 mm (0.0015 in). The ribbon cables 70′, 70″, and 70′″ may be secured within the grooves 64, 66, and 68 by application of a heat shrink polyolefin tube around the outside of tubular member 56. Windows may be formed by ablating the heat shrink tube locally over the electrodes 48, 50 using a CO2 laser. As such, any of the leads 76 may be uninsulated at a point along the length of catheter 12 and coupled to an electrode 48, 50, such as, for example, a flexible foil electrode or an electrode formed according to any of the embodiments described herein and exposed through a window 44, 46 of catheter 12.
[0074] In one example, connector feed 72 may include approximately 8 electrical leads in a ribbon cable, and ribbon cables 70′, 70″, and 70′″ may include enough electrical leads 76 to send electrical signals to each electrode 48, 50 of the proximal electrode assemblies 14 and distal electrode assemblies 16. For instance, connector feed 72 may include an electrical lead for each of power, ground, data stream, anode signal, cathode signal, and leads to send and receive signals from various elements in catheter 12. Ribbon cables 70 connect to each electrode 48, 50 of the electrode assemblies 14, 16 in order to stimulate the targeted nerves.
[0075] ASIC 74 may serve to direct the signals received from connector feed 72. For example, based on the received signals, ASIC 74 may direct electrical signals to one or a plurality of the electrodes 48, 50 of the proximal electrode assemblies 14 and the distal electrode assemblies 16. As such, there may be only one connection and/or connector at the proximal end of catheter 12 to transmit electrical or other signals distally from, for example, control unit 30, to the proximal and distal electrode assemblies 14 and 16, providing further space within tubular member 56 for the fluid lumens 60 and 62, additional medical instruments, and/or allowing the tubular member 56 and the remainder of the catheter 12 to be smaller. ASIC 74 allows for a reduction in conductors in the connector feed 72, and thus reduces the number of couplings between connector feed 72 and ASIC 74, improving reliability and reducing cost. Moreover, ASIC 74 permits the use of a connector with 8 or 9 pins, rather than a connector with 19 pins, further improving reliability and reducing the risk of signal interference or misalignment.
[0076] FIG. 5 illustrates a schematic view of the connector feed 72, ASIC 74, ribbons cables 70′, 70″, 70′″, and the electrode assemblies 14, 16. Ribbon cables 70′, 70″, 70′″ may be three separate ribbon cables, or may be one ribbon cable that branches out into three ribbon cables. As discussed, connector feed 72 may include 8 conductor leads 54 connected to ASIC 74. ASIC 74 connects to ribbon cables 70′, 70″, 70′″ to selectively deliver signals to one or a plurality of the proximal electrodes 48 or the distal electrodes 50. Proximal electrodes 48 and distal electrodes 50 may be mounted or otherwise physically and electrically connected to the corresponding ribbon cable 70′, 70″, 70′″. In one example, ribbon cables 70′, 70″, 70′″ may include one lead 76 per electrode 48, 50, with the particular lead 76 terminating in an uninsulated portion where the lead 76 is coupled to the electrode 48, 50 by mechanical rivet, solder, crimping, or another technique.
[0077] As shown in FIGS. 4 and 5 , one ribbon cable 70′ may include one proximal electrode assembly 14 with six proximal electrodes 48. One ribbon cable 70″ may include one proximal electrode assembly 14 with six proximal electrodes 48 and one distal electrode assembly 16 with three distal electrodes 50. One ribbon cable 70′″ may include one distal electrode assembly 16 with three distal electrodes 50. ASIC 74 may decode the signals from connector feed 72 and determine if a particular electrode 48, 50 is to be an anode or a cathode, so each of the ribbon cables 70′, 70″, 70′″ may only require one lead for each of the electrodes 48, 50 connected to that ribbon cable 70′, 70″, 70′″. In this situation, ribbon cable 70′ may include six leads 76 to connect to the six proximal electrodes 48. Ribbon cable 70″ may include nine leads 76 to connect to the six proximal electrodes 48 and three distal electrodes 50. Ribbon cable 70′″ may include as few as three leads 76. The proximal electrodes 48 of the two proximal electrode assemblies 14 may be aligned (positioned at the same axial position and different circumferential positions), and the distal electrodes 50 of the two distal electrode assemblies 16 may be displaced (positioned at different axial positions and different circumferential positions). The electrodes 48, 50 may also take different orientations and arrangements in order to locate and/or stimulate the target nerves.
[0078] FIG. 6 illustrates an axial cross-sectional view of a proximal portion of the catheter 12, including tubular member 56 and an outer layer or sheath 75, at a position of proximal electrode assemblies 14. As shown, guide wire lumen 58, fluid lumens 60 and 62, and grooves 64, 66, and 68 longitudinally pass through tubular member 56. Ribbon cables 70′, 70″, and 70′″ with leads 76 are positioned within grooves 64, 66, and 68. Proximal electrodes 48 are mounted over ribbon cables 70′ and 70″ and are exposed through proximal windows 44. Although not shown, distal electrodes 50 are mounted and/or connected to ribbon cables 70″ and 70′″ and exposed through distal windows 46 in a similar manner to the proximal electrodes 48.
[0079] In another aspect of this disclosure, the tubular member 56 may include printed ink conductors and electrodes similar to that shown in FIG. 3 . In this example, the printed ink conductors may extend distally from ASIC 74 and branch out in a similar manner as discussed above, but with the printed ink conductors extending along the circumferential surface of the tubular member 56. The printed ink conductors may connect to printed electrodes, and signals may be selectively transmitted via the ASIC 74 to the electrodes through the printed ink conductors.
[0080] Tubular member 56 may be extruded polyurethane (or any other suitable biocompatible material). Sheath 75 fitting over tubular member 56 may be made of any biocompatible plastic or other material. In one aspect, sheath 75 is a 0.002 m thick polyolefin shrink tube that may be positioned around tubular member 56 and shrunk down using a heat gun or other heating source. Windows 44 may be formed by ablating the heat shrink tube locally over the electrodes 48, 50 using a CO2 laser. Alternatively, sheath 75 may be a 3-D printed insulation layer with windows 44 over electrodes 48, 50 formed by open portions during the 3-D printing.
[0081] FIG. 7A illustrates a longitudinal cross-sectional view of a portion of one groove 66 in the tubular member 56, and FIG. 7B illustrates an exploded view of a portion of a ribbon cable 70″ that may fit within groove 66. The configuration in FIG. 7A shows an arrangement where electrode 48 is coupled at one end of the electrode to the appropriate lead 76 of ribbon cable 70″ and corrugations 82 in ribbon cable 70″ pass beneath electrode 48. Such an arrangement may be used if the distance between electrodes 48, 50 is short, and using as many corrugations as possible provides maximum longitudinal and rotational flexibility for the ribbon cables 70′, 70″, and 70′″ in the catheter. Alternatively or additionally, as in FIG. 7B , corrugations 82 in ribbon cables 70′, 70″, and 70′″ may be located between electrodes only, and not under the electrodes
[0082] As shown in FIG. 7A , ribbon cable 70″ may be coupled to proximal electrode 48 via a connection 80. Connection 80 electrically and physically connects electrode 48 to the appropriate lead 76 of ribbon cable 70″ that corresponds to electrode 48. Connection 80 may be, for example, a wire connection with solder or a rivet. Electrode 48 may longitudinally overlap with ribbon cable 70″, and may extend longitudinally and be positioned radially underneath a portion of tubular member 56. A portion of electrode 48 may be exposed through window 44 and may be partially covered by a non-insulating and/or conductive cover 49.
[0083] Proximal electrode 48 may be exposed via proximal window 44 in sheath 75. A proximal electrode 48, along with the other electrodes 48, 50, may be a sheet Platinum-Iridium (Ptlr) electrode with a thickness of approximately 0.0381-0.0508 mm (0.0015-0.002 in). Ribbon cable 70″ may be coupled to the other proximal electrodes 48 and the distal electrodes 50 in the same manner as illustrated in FIG. 7A . Electrodes 48, 50 may be various other known electrode assemblies, for example, ring electrodes fixed to the exterior of catheter 12. Electrodes 48, 50 may also be formed of other conductive materials, including platinum, gold, stainless steel, titanium nitride, MP35N, palladium, or another appropriate material. Electrodes 48, 50 may also be coupled to ribbon cables 70′, 70″, and 70′″ with conductive adhesive, heat fusion, crimping, riveting, microwelding, or another appropriate method. Electrodes 48, 50 may also include an insulating coating over a portion of the electrodes 48, 50 that may facilitate directional targeting of one or more nerves.
[0084] Each ribbon cable 70′, 70″, and 70′″ may also include corrugations 82 within at least one or more portions of grooves 64, 66, and 68. Corrugations 82 may provide greater longitudinal and lateral flexibility and bendability of the catheter 12 and the internal components. Corrugations 82 may pass underneath an electrode 48, as shown in FIG. 7A . Alternatively or additionally, corrugations 82 may be positioned along ribbon cables 70′, 70″, and 70′″ between longitudinally adjacent electrodes 48, 50, as shown in FIG. 7B . In this aspect, a filler block 84 may support electrode 48, 50 and ribbon cable 70″. A filler strip 86 may include contours 88 that mirror the corrugations 82. Contours 88 may extend radially inwardly to fit within corrugations 82. Filler strip 86 may be positioned on a radially outward side of ribbon cable 70″ to support the corrugations 82 of ribbon cable 70″ between electrodes 48, 50. Corrugations 82 of ribbon cable 70″ may be unsupported or open on the radially inward side of corrugations opposite to filler strip 86 and contours 88, which may increase the longitudinal or lateral flexibility. Filler blocks 84 and filler strips 86 may be elastomeric and may be sized to fit within grooves 64, 66, and 68 of tubular member 56.
[0085] FIGS. 8-10 illustrate an alternative embodiment of the disclosure, including tubular member 100 and helical ribbon cable 101 that may be radially surrounded by an outer layer, sleeve, or sheath 175 to form a catheter 112 to stimulate target nerves as discussed above, according to another aspect of this disclosure.
[0086] FIG. 8 illustrates a portion of tubular member 100. Tubular member 100 is sized to fit within sheath 175 in a similar manner to tubular member 56 (FIG. 10 ). Tubular member 100 includes a series of lumens 102, which may include a guide wire lumen and fluid lumens that may function as discussed above. Tubular member 100 includes a radial extension 104. Radial extension 104 extends radially outward from tubular member 100. Radial extension 104 may be integrally formed of the same material as tubular member 100, or may be a separate element attached to or positioned around tubular member 100. Radial extension 104 may helically extend along an outer surface of tubular member 100 and include a helical pitch 106. Electrode locations 108 may be located such that there are at least portions of radial extension 104 between electrode locations 108, as shown in FIG. 8 , to form an electrode pitch 110. One or both of tubular member 100 and radial extension 104 may be formed by, for example, extrusion, molding, or 3-D printing using XYZ and rotary motions to deposit a flexible polymer around a mandrel, with some or all of the polymer being sacrificial.
[0087] FIG. 9 illustrates a portion of helical ribbon cable 101 with electrodes 114 mounted on helical ribbon cable 101. FIG. 9 shows a top view of cable 101 in a straight, flat configuration prior to its placement around tubular member 100. Helical ribbon cable 101 may be formed and may function similarly to ribbon cables 70′, 70″, and 70′″ with leads 76 surrounded by non-conducting material 78 as discussed above. Additionally, electrodes 114 may be coupled to ribbon cable 101 as with electrodes 48, 50 and ribbon cables 70′, 70″, and 70′″. Helical ribbon cable 101 may include an upper conductor 103 having multiple leads that communicate with the upper electrodes 114, and a lower conductor 105 also having multiple leads communicating with the lower electrodes 114. Conductors 103 and 105 are surrounded by and separated by insulating layers 107.
[0088] Electrodes 114 are mounted on helical ribbon cable 101 at an angle to the axis of the helical ribbon cable 101 such that the electrodes lie at the correct axially disposed angle when the helical ribbon cable 101 is wrapped around the tubular member 100 in the helical recess defined by radial extensions 104. After wrapping the helical ribbon cable 101 around the tubular member, the electrodes 114 adopt the alignment shown by locations 108 in FIG. 8 . In one example, if the electrodes 114 are to be oriented with the electrodes' shorter dimension disposed circumferentially around the tubular member 100 after helical ribbon cable 101 is helically wrapped, then electrodes 114 may be mounted on helical ribbon cable 101 at approximately a 59 degree angle relative to a longitudinal axis of the helical ribbon cable 101. The length of helical ribbon cable 101 between paired electrodes 114 corresponds to an electrode pitch 110 between paired electrode locations 108. Therefore, when the helical ribbon cable 101 is wrapped around tubular member 100 between radial extensions 104, paired electrodes 114 align with electrode locations 108. For example, if the electrode pitch 110 is about 10 mm, and the tubular member 100 has an outside diameter of about 3.2 mm, then the distance between sets of paired electrodes on helical ribbon cable 101 is approximately 23 mm.
[0089] As shown in FIG. 10 , catheter 112 may include tubular member 100 and helical ribbon cable 101 positioned within sheath 175. Electrodes 114 and helical ribbon cable 101 may function as discussed above, without interfering with lumens 102 and other radially internal elements of tubular member 100. Moreover, electrodes 114 may be electrically and physically coupled to helical ribbon cable 101 via connection 116. Connection 116 may be, for example, a wire connection, a solder connection, a rivet, or another mechanical and electrical connection to mechanically and electrically connect electrode 114 to helical ribbon cable 101. Electrodes 114 may then be exposed via an electrode window 118. Sheath 175 may also radially surround tubular member 100, and sheath 175 may comprise one or more insulating layers of flexible polyimide, shrink tubing, and/or a flexible filler.
[0090] FIG. 11 illustrates an aspect of the present disclosure that may be incorporated in any of the foregoing aspects. As shown in FIG. 11 , each electrode 114 may be coupled to a small ASIC 120. For example, helical ribbon cable 101 may be coupled to a tubular member 100A as part of a catheter 112A. Tubular member 100A may include guide wire lumen 58, two fluid lumens 60 and 62, and grooves 64, 66, and 68, similar to as shown in FIG. 4 . Small ASICs 120 may be positioned within grooves 64, 66, and 68 radially between electrodes 48, 50 and guidewire lumen 58. The small ASICs 120 allow for a reduction of conductive leads 76. For example, unless an ASIC 120 is located locally for each electrode 48, 50, there must be a separate lead 76 for each electrode 48, 50. With an ASIC 120 specific to each electrode, the ASIC 120 may decode a signal from a control unit and determine whether the signal applies to that particular electrode 48, 50. Therefore, helical ribbon cable 101, or other ribbon cable in other aspects of this disclosure, would be connected through the electrode-specific ASICs 120 to all electrodes 48, 50, and the helical ribbon cable 101 would only need five conductive leads 76 (an anode reference, a cathode reference, a power, a ground, and a data line) for any number of electrodes 48, 50. It is further noted that locally located ASICs 120 require a groove or recess in the tubular member 100A, but may also be incorporated in other tubular members or catheters of this disclosure. For instance, grooves or recesses may be extruded in tubular member 100A, and tubular member 100A may be extruded, 3-D printed, or otherwise formed to include helical lumens such that the grooves or recesses do not interfere with the lumens. Grooves or recesses may also be helical, and the helical grooves or recesses, along with helical lumens, may be formed by extruding the tubular member as with longitudinal grooves, and lumens, and then heat setting the tubular member in a twisted state. Each electrode 114 may be exposed through a window (similar to as shown in FIG. 10 ), or may be partially covered by a non-insulating and/or conductive element 121, as shown in FIG. 11 .
[0091] Once positioned within a patient, the catheter 112A of FIG. 11 , with helical ribbon 101 and small ASICs 120, may be used to stimulate the target nerves as discussed above. In particular, the conductive leads of the helical ribbon cable 101 may be reduced because each lead of the same helical ribbon cable 101 may connect to each small ASIC 120. Based on the signals through the leads of the helical ribbon cable 101, each small ASIC 120 controls whether the electrical signals through leads are emitted through the particular electrodes 114. Similar to the example shown in FIGS. 4-6 , the catheter 112A of FIG. 11 may only include one connection at the proximal end of catheter 112A to transmit electrical or other signals distally to the proximal and distal electrode assemblies 14 and 16, providing further space within tubular member 100A for the fluid lumens 60 and 62, additional medical instruments, and/or allowing the tubular member 100A and catheter 112A to be smaller.
Wireless Connections to Control Unit
[0092] FIG. 12 illustrates an alternative medical system 210 with similar elements to the medical system 10 of FIG. 1 shown by 200 added to the reference numbers. Medical system 210 includes a wireless connection from control unit 230 to catheter 212. Catheter 212 may be inserted and positioned as discussed with respect to FIG. 1 . Catheter 212 may include proximal and distal electrode assemblies 214, 216 that are exposed through proximal and distal windows as discussed above.
[0093] Instead of proximal connector 32, catheter 212 may include a manifold or hub 211 at a proximal end or coupled to the proximal end of catheter 212. Hub 211 may be positioned external to the patient when catheter 212 is inserted. Hub 211 may include a plurality of lumens that may connect to the guide wire and fluid lumens within catheter 212. In one aspect, hub 211 may be connected to a fluid port 213 and a wireless unit 215. Fluid port 213 may include one lumen connected through hub 211 to a lumen in catheter 212, or fluid port 213 may include a plurality of lumens connected through hub 211 to lumens within catheter 212, including a guide wire port. Wireless unit 215 may include a battery and a receiver/transmitter. The receiver/transmitter of wireless unit 215 may be in wireless communication with control unit 230, via, for example, a Bluetooth connection. As such, control unit 230 may send signals to and receive signals from wireless unit 215. Wireless unit 215 may then be coupled to one or more leads or ribbon cables to transmit electrical signals distally to the proximal and distal electrode assemblies 214, 216, and the signals may be distributed via one or more ASICs within catheter 212 to stimulate a target nerve.
[0094] Wireless unit 215, or catheter 212 itself, may also include a wireless information unit (not shown), for example, an RFID tag or wireless chip, or other unique coded information related to the catheter 212 including, for example, the catheter serial number and construction change level. For instance, as improvements to the catheter are made over time, each improvement is recorded as a change level. This change level may, for example, include an electrode material change or an electrode surface finish. These changes may permit the use of a more effective stimulation pulse stream. The control unit 230 may evaluate the change level code and determine whether a new stimulation program installed on the control unit 230 is applicable to that catheter 210, as the software of control unit 230 may also be updated periodically. The change level code may avoid the creation of “generic” pirated clones by detecting false codes and preventing the system from operating if a false code is detected. As such, this would also reduce the risks to the patient, medical professional, and manufacturer by eliminating the risk of inferior devices being improperly used without the proper clinical testing and approval. The wireless information unit may further record usage data for catheter 212, including, for example, time of day of use, duration of use, number of times used, and other information related to communications from control unit 230. Hub 211 with wireless unit 215 does not require a wired connection between the control unit 230 and the catheter 212, reducing the assembly time for a medical professional and reducing the risk of signal interference, misalignment, cable snagging, and other human errors.
[0095] Alternatively, though not shown, wireless unit 215 may receive all data wirelessly from control unit 230, but the low voltage power necessary for the receiver in wireless unit 215 may be delivered by a low-cost three conductor cable from the control unit 230. This arrangement allows the system to operate for long periods of time without the risk of running low on battery power. Although this arrangement requires a cable for power, the arrangement nevertheless results in a minimal number of pins in the connections to the control unit, thereby enhancing reliability and reducing the risk of misalignment.
Radiopaque Catheters and Orientation Indicators
[0096] FIGS. 13 and 14 illustrate an alternative catheter 312 with similar elements to the catheter 12 of FIG. 1 shown by 300 added to the reference numbers. Aspects shown in FIGS. 13 and 14 may be incorporated in any of the foregoing catheter examples in order to ensure that the catheter 312 is aligned properly. As shown in FIG. 13 , catheter 312 may be radiopaque and may be viewed via one or more imaging systems, for example, via fluoroscopy, X-ray, or other imaging methods. Catheter 312 may be made to be radiopaque by using a polymer that is approximately 20% BaSO4, or by printing radiopaque ink on the exterior of the catheter. Radiopaque catheter 312 may include two proximal electrode assemblies 314, each with six proximal electrodes 348 exposed via proximal windows 344, and two distal electrode assemblies 316, each with three distal electrodes 350 exposed via distal windows 346. Electrodes 348, 350 may also be radiopaque, for example, containing 10% Platinum-Iridium (PtIr), and may appear to be darker than the radiopaque catheter 312.
[0097] FIG. 13 shows an anterior view of radiopaque catheter 312 properly aligned such that proximal electrodes 348 face substantially posteriorly (to the patient's back) to stimulate the left phrenic nerve 26, and distal electrodes 350 face substantially laterally (to the patient's right) to stimulate the right phrenic nerve 28. When viewed anteriorly, the proximal electrodes 348 may appear in two aligned rows of six electrodes in the center of the catheter 312. The distal electrodes 350 may appear in a single row of six electrodes positioned toward the lateral (patient's right) edge of the catheter 312. Moreover, the proximal electrodes 348 and three alternating distal electrodes 350 may appear to be darker than the catheter shaft 312, even though these electrodes are posterior facing. Three alternating distal electrodes 350 may appear to be even darker than the other electrodes as these electrodes are anterior facing. If the catheter 312 and electrodes 348, 350 appear differently than shown and described, the catheter 312 and electrodes 348, 350 are likely improperly positioned. As such, a medical professional may use this visualization to ensure that the catheter 312 and electrodes 348, 350 are positioned properly when stimulating or preparing to stimulate target nerves.
[0098] FIG. 14 illustrates an additional example of catheter 312 that is radiopaque and may aid in ensuring the catheter 312 and electrodes 348, 350 are properly positioned. As with FIG. 13 , when viewed anteriorly via an imaging system, a properly positioned catheter 312 may include two rows of six proximal electrodes 348 in the center of the catheter 312, and one row of six distal electrodes 350 toward the lateral (patient's right) edge of the catheter 312. The proximal electrodes 348 and three alternating distal electrodes 350 may appear darker than the catheter 312, and three alternating distal electrodes 350 may appear even darker than the other electrodes.
[0099] As shown in FIG. 14 , catheter 312 may further include one or more radiopaque markers 321. For example, catheter 312 may include a one radiopaque marker 321 at a distal end of the catheter 312, and one radiopaque marker 321 at a proximal end of the catheter 312. Radiopaque markers 321 may be formed by printing or otherwise applying radiopaque ink to the catheter 312. When viewed with an imaging system, the orientation and/or appearance of the radiopaque markers 321 may allow a medical professional to determine whether the catheter 312 is properly positioned and/or oriented. For example, the distal radiopaque marker 321 may be a check mark, and the proximal radiopaque marker 321 may be a smiley face, as shown in FIG. 14 . When viewed anteriorly, if the checkmark is longer on the right side, and the smiley face is right-side up, then the catheter 312 is properly oriented. Otherwise, orientation is not proper, and the user may adjust the position of catheter 312.
[0100] Catheter 312 may include a further radiopaque orientation marker, for example, orientation stripe 323. Orientation stripe 323 may extend longitudinally along at least a portion of the length of the catheter 312 such that when viewed anteriorly with an imaging system, the orientation stripe 323 passes through the middle of the catheter 312. Orientation stripe 323 may bisect or align with a midpoint of the radiopaque markers 321. Orientation stripe 323 may be positioned on catheter 312 such that, when the catheter 312 and electrodes 348, 350 are properly positioned and viewed anteriorly using an imaging system, orientation stripe 323 passes evenly between the two rows of proximal electrodes 348 and passes to the medial (patient's left) side of the one row of distal electrodes 350. Orientation stripe 323 may be formed during the formation of the catheter 312, for example, during an extrusion. Orientation stripe 323 may include a different color or pattern, may be laser marked, may be printed with radiopaque ink, may be a radiopaque wire introduced into a dedicated lumen of the catheter body, or may be formed by any other appropriate methods. If the catheter 312 is not properly positioned, the catheter 312 may be adjusted until the electrodes 348, 350, radiopaque markers 321, and orientation stripe 323 appear when viewed anteriorly as illustrated in FIG. 14 .
[0101] Orientation stripe 323 may be also be used to control the orientation of the catheter 312 while inserting catheter 312 into a patient without taking an x-ray or using another visualization technique. For example, orientation stripe 323 may run longitudinally from the distal end to the proximal end of catheter 312. Therefore, as long as the catheter 312 is not undergoing torsion, a medical professional is able to determine the orientation of the distal end, which is inserted into the patient and thus not visible without imaging technology, by observing the location of the orientation stripe 323 on the proximal end that extends proximally from the patient.
[0102] Radiopaque catheter 312 may also include an orientation hub 325. For example, the shape and size of orientation hub 325 may be such that orientation hub may be sutured or otherwise attached in only one orientation. Orientation hub 325 may have an apex 327 that circumferentially aligns with orientation stripe 323 on catheter 312, and which is opposite to a flat bottom that may rest on a patient's chest or another surface. The flat bottom may also include two attachment members or suture tabs 329 extending from the bottom such that the bottom may be coupled to other elements in the proper orientation. Additionally or alternatively, orientation hub 325 may include a wireless unit as discussed above with respect to FIG. 12 .
[0103] Catheter 312 may include all or a portion of the aforementioned positioning markers. Additionally, a medical professional may use different positioning markers to ensure the catheter 312 is positioned properly as different markers may exhibit greater visibility depending on the patient, the imaging system, and other variables. Catheter 312 and the various positioning and orientation markers may be modified and/or customized depending on the patient. For example, fewer electrodes 348, 350 may be used with a smaller patient, for example, a neonate. Alternatively, a patient with abnormal nerve locations may require a different catheter orientation and/or arrangement.
Other Alternative Embodiments and Interpretation of Terms
[0104] As noted earlier, any of the components and features of any of the embodiments disclosed herein may be combined and used in any suitable combinations with any of the other components and features disclosed herein. However, for the sake of example, some ways in which the described example embodiments may be varied include:
-
- [0105] different numbers of electrodes;
- [0106] different electrode configurations;
- [0107] different electrode fixing (crimp, adhesive, microweld, rivet, etc.);
- [0108] different electrode shape (round, oval, circular, rectangular, etc.);
- [0109] different electrode material;
- [0110] different electrode surface areas;
- [0111] different electrode spacing;
- [0112] different number or shapes of lumens;
- [0113] different window shape/dimensions;
- [0114] different catheter profile (e.g., +/−9 Fr);
- [0115] different catheter length; and/or
- [0116] different steering mechanism.
[0117] As mentioned above, the use of the various catheter embodiments allows for an increase in the number of available lumens within the catheter. The size of the catheter may also be reduced, for example, for use in neonatal patients or patients who require a smaller catheter. Ribbon cables increase the longitudinal flexibility of the catheter and the electrode connections during the manipulation and use of the catheter. Using ASICs and/or wireless connections reduces the number of cables and connections the medical professional must properly connect and avoid during various procedures, while still properly and accurately stimulating various internal nerves. Additionally, radiopaque catheters, radiopaque electrodes, radiopaque markers, and orientation markers may aid a medical professional in locating the position of the catheter and orienting the catheter in order to most effectively stimulate the patient's nerves.
[0118] Unless the context clearly requires otherwise, throughout the description and the claims:
-
- [0119] “comprise,” “comprising,” and the like are to be construed in an inclusive sense, as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”;
- [0120] “connected,” “coupled,” or any variant thereof, means any connection or coupling, either direct or indirect, between two or more elements; the coupling or connection between the elements can be physical, electrical, or a combination thereof;
- [0121] “herein,” “above,” “below,” and words of similar import, when used to describe this specification, shall refer to this specification as a whole, and not to any particular portions of this specification;
- [0122] “or,” in reference to a list of two or more items, covers all of the following interpretations of the word: any of the items in the list, all of the items in the list, and any combination of the items in the list; and
- [0123] the singular forms “a,” “an,” and “the” also include the meaning of any appropriate plural forms.
[0124] Words that indicate directions such as “vertical,” “transverse,” “horizontal,” “upward,” “downward,” “forward,” “backward,” “inward,” “outward,” “left,” “right,” “front,” “back,” “top,” “bottom,” “below,” “above,” “under,” and the like, used in this description and any accompanying claims (where present), depend on the specific orientation of the apparatus described and illustrated. The subject matter described herein may assume various alternative orientations. Accordingly, these directional terms are not strictly defined and should not be interpreted narrowly.
[0125] Specific examples of systems, methods and apparatus have been described herein for purposes of illustration. These are only examples. The technology provided herein can be applied to systems other than the example systems described above. Many alterations, modifications, additions, omissions, and permutations are possible within the practice of this invention. This invention includes variations on described embodiments that would be apparent to the skilled addressee, including variations obtained by: replacing features, elements and/or acts with equivalent features, elements and/or acts; mixing and matching of features, elements and/or acts from different embodiments; combining features, elements and/or acts from embodiments as described herein with features, elements and/or acts of other technology; and/or omitting combining features, elements and/or acts from described embodiments.
[0126] It is therefore intended that the following appended claims and claims hereafter introduced are interpreted to include all such modifications, permutations, additions, omissions, and sub-combinations as may reasonably be inferred. The scope of the claims should not be limited by the preferred embodiments set forth in the examples, but should be given the broadest interpretation consistent with the description as a whole.
Claims
Certificate of Correction present
The claims shown below may not include correction changes. Use the corrected PDF for authoritative text.
We claim:
1. A catheter, comprising:
an outer sheath defining a plurality of apertures therethrough;
a body defining at least one longitudinal lumen therein, wherein at least a portion of the body is radially inward of the outer sheath, and the apertures are radially outward of the lumen;
a plurality of electrodes positioned in or on the catheter, each electrode being electrically exposed through an aperture of the plurality of apertures; and
a ribbon cable extending through the lumen and including a plurality of leads, the plurality of leads being electrically connected to the plurality of electrodes,
wherein the plurality of apertures includes a plurality of proximal apertures and a plurality of distal apertures, the plurality of proximal apertures including two longitudinally extending rows of proximal apertures, and wherein the outer sheath includes (1) a first radiopaque feature at a distal portion of the sheath for confirming an orientation of the distal apertures and (2) a second radiopaque feature at a proximal portion of the sheath and positioned circumferentially opposite to a line extending between the two rows of proximal apertures.
2. The catheter of claim 1, wherein the lumen is a groove exposed along the circumference of the body along at least a portion of the length of the body, the groove being at least partially covered by the outer sheath.
3. The catheter of claim 1, wherein the plurality of leads are at least partially surrounded by a non-conducting material; and wherein the ribbon cable is electrically connected to at least one electrode via a connection.
4. The catheter of claim 1, wherein the ribbon cable includes a plurality of corrugations.
5. The catheter of claim 4, further including at least one filler positioned within at least a portion of the corrugations, and wherein the corrugations are positioned radially inward of at least one electrode.
6. The catheter of claim 1, further including: at least one fluid lumen and a guide wire lumen, and a connector feed and an application specific integrated circuit radially inward or outward of the outer sheath, wherein the application specific integrated circuit connects the connector feed to the ribbon cable.
7. The catheter of claim 6, wherein the ribbon cable includes three branches of ribbon cable;
wherein the at least one longitudinal lumen includes three longitudinal lumens spaced circumferentially around an exterior of the body and radially inward of the outer sheath; and
wherein the three branches extend distally from the application specific integrated circuit, and each of the three branches connects to at least one electrode through a corresponding longitudinal lumen.
8. The catheter of claim 7, wherein one branch of the three branches includes at least one lead that electrically connects at least one proximal electrode and at least one other lead that electrically connects at least one distal electrode.
9. The catheter of claim 1,
wherein the plurality of distal apertures includes two longitudinally extending rows comprising a first row of distal apertures and a second row of distal apertures; and
wherein one row of the two rows of proximal apertures is circumferentially aligned with the first row of distal apertures.
10. The catheter of claim 9, wherein the first radiopaque feature is for confirming an orientation of the first row of distal apertures relative to the second row of distal apertures.
11. The catheter of claim 9, wherein the other of the two rows of proximal apertures is circumferentially offset from both the first row of distal apertures and the second row of distal apertures.
12. The catheter of claim 10, further including a hub, wherein the hub includes an orientation feature and a port, wherein the port is configured to couple the hub to a proximal portion of the catheter in a particular orientation.
13. The catheter of claim 1, wherein the lumen and the ribbon cable are recessed from an outer surface of the body.
14. The catheter of claim 1, wherein the lumen is a first lumen, and the ribbon cable is a first ribbon cable, and wherein the catheter further comprises a second ribbon cable extending through a second lumen defined by the body.
15. The catheter of claim 14, wherein the first lumen and the second lumen are spaced circumferentially around an exterior of the body.
16. The catheter of claim 1, wherein the ribbon cable includes three or more leads arranged in a row.
17. The catheter of claim 1, wherein the ribbon cable has a single, flexible planar structure.
18. The catheter of claim 1, wherein the outer sheath has an inner surface exposed to the at least one longitudinal lumen and an outer surface comprising the outermost surface of at least a portion of the catheter.
19. A catheter, comprising:
an outer sheath defining a plurality of apertures therethrough;
a body defining at least one lumen recessed within an outer surface of the body, wherein the apertures are radially outward of the lumen, and wherein an inner surface of the sheath is exposed to the ribbon cable, and an outer surface of the sheath is the outermost surface of at least a portion of the catheter;
a plurality of electrodes positioned in or on the catheter, each electrode being electrically exposed through an aperture of the plurality of apertures; and
a ribbon cable extending through the lumen, in a single flexible planar configuration, and including at least three leads arranged in a row, the plurality of at least three leads being electrically connected to the plurality of electrodes.
20. The catheter of claim 19, wherein the lumen is a first lumen, and the ribbon cable is a first ribbon cable, and wherein the catheter further comprises a second ribbon cable extending through a second lumen defined by the body.
21. The catheter of claim 19, wherein the lumen is a groove exposed along the circumference of the body along at least a portion of the length of the body, the groove being at least partially covered by the outer sheath.
22. The catheter of claim 19, wherein the plurality of apertures includes a first row of proximal apertures, a second row of proximal apertures, a first row of distal apertures, and a second row of distal apertures, and wherein the first row of proximal apertures is circumferentially aligned with one of either the first row of distal apertures or the second row of distal apertures, and the second row of proximal apertures is circumferentially offset from both the first row of distal apertures and the second row of distal apertures.
Patent Citations (679)
| Patent | Date | Inventor | Cited By |
|---|---|---|---|
| US1693734(A) | 1928-12-01 | Waggoner | Applicant |
| US2532788(A) | 1950-12-01 | Sarnoff | Applicant |
| US2664880(A) | 1954-01-01 | Wales, Jr. | Applicant |
| US3348548(A) | 1967-10-01 | Chardack | Applicant |
| US3470876(A) | 1969-10-01 | John | Applicant |
| US3769984(A) | 1973-11-01 | Muench | Applicant |
| US3804098(A) | 1974-04-01 | Friedman | Applicant |
| US3817241(A) | 1974-06-01 | Grausz | Applicant |
| US3835864(A) | 1974-09-01 | Rasor et al. | Applicant |
| US3847157(A) | 1974-11-01 | Caillouette et al. | Applicant |
| US3851641(A) | 1974-12-01 | Toole et al. | Applicant |
| US3896373(A) | 1975-07-01 | Zelby | Applicant |
| US3938502(A) | 1976-02-01 | Bom | Applicant |
| US3983881(A) | 1976-10-01 | Wickham | Applicant |
| US4054881(A) | 1977-10-01 | Raab | Applicant |
| US4072146(A) | 1978-02-01 | Howes | Applicant |
| US4114601(A) | 1978-09-01 | Abels | Applicant |
| US4173228(A) | 1979-11-01 | Childress et al. | Applicant |
| US4249539(A) | 1981-02-01 | Mezrich et al. | Applicant |
| US4317078(A) | 1982-02-01 | Weed et al. | Applicant |
| US4380237(A) | 1983-04-01 | Newbower | Applicant |
| US4407294(A) | 1983-10-01 | Vilkomerson | Applicant |
| US4416289(A) | 1983-11-01 | Bresler | Applicant |
| US4431005(A) | 1984-02-01 | McCormick | Applicant |
| US4431006(A) | 1984-02-01 | Trimmer et al. | Applicant |
| US4445501(A) | 1984-05-01 | Bresler | Applicant |
| USRE31873(E) | 1985-04-01 | Howes | Applicant |
| US4573481(A) | 1986-03-01 | Bullara | Applicant |
| US4586923(A) | 1986-05-01 | Gould et al. | Applicant |
| US4587975(A) | 1986-05-01 | Salo et al. | Applicant |
| US4643201(A) | 1987-02-01 | Stokes | Applicant |
| US4674518(A) | 1987-06-01 | Salo | Applicant |
| US4681117(A) | 1987-07-01 | Brodman et al. | Applicant |
| US4683890(A) | 1987-08-01 | Hewson | Applicant |
| US4697595(A) | 1987-10-01 | Breyer et al. | Applicant |
| US4706681(A) | 1987-11-01 | Breyer et al. | Applicant |
| US4771788(A) | 1988-09-01 | Millar | Applicant |
| US4819662(A) | 1989-04-01 | Heil, Jr. et al. | Applicant |
| US4827935(A) | 1989-05-01 | Geddes et al. | Applicant |
| US4830008(A) | 1989-05-01 | Meer | Applicant |
| US4840182(A) | 1989-06-01 | Carlson | Applicant |
| US4852580(A) | 1989-08-01 | Wood | Applicant |
| US4860769(A) | 1989-08-01 | Fogarty et al. | Applicant |
| US4905698(A) | 1990-03-01 | Strohl, Jr. et al. | Applicant |
| US4911174(A) | 1990-03-01 | Pederson et al. | Applicant |
| US4934049(A) | 1990-06-01 | Kiekhafer et al. | Applicant |
| US4944088(A) | 1990-07-01 | Doan et al. | Applicant |
| US4951682(A) | 1990-08-01 | Petre | Applicant |
| US4957110(A) | 1990-09-01 | Vogel et al. | Applicant |
| US4989617(A) | 1991-02-01 | Memberg et al. | Applicant |
| US5005587(A) | 1991-04-01 | Scott | Applicant |
| US5036848(A) | 1991-08-01 | Hewson | Applicant |
| US5042143(A) | 1991-08-01 | Holleman et al. | Applicant |
| US5056519(A) | 1991-10-01 | Vince | Applicant |
| US5115818(A) | 1992-05-01 | Holleman et al. | Applicant |
| US5146918(A) | 1992-09-01 | Kallok et al. | Applicant |
| US5170802(A) | 1992-12-01 | Mehra | Applicant |
| US5184621(A) | 1993-02-01 | Vogel et al. | Applicant |
| US5224491(A) | 1993-07-01 | Mehra | Applicant |
| US5243995(A) | 1993-09-01 | Maier | Applicant |
| US5265604(A) | 1993-11-01 | Vince | Applicant |
| US5267569(A) | 1993-12-01 | Lienhard | Applicant |
| US5314463(A) | 1994-05-01 | Camps et al. | Applicant |
| US5316009(A) | 1994-05-01 | Yamada | Applicant |
| US5324322(A) | 1994-06-01 | Grill, Jr. et al. | Applicant |
| US5330522(A) | 1994-07-01 | Kreyenhagen | Applicant |
| US5345936(A) | 1994-09-01 | Pomeranz et al. | Applicant |
| US5383923(A) | 1995-01-01 | Webster, Jr. | Applicant |
| US5411025(A) | 1995-05-01 | Webster, Jr. | Applicant |
| US5417208(A) | 1995-05-01 | Winkler | Applicant |
| US5451206(A) | 1995-09-01 | Young | Applicant |
| US5456254(A) | 1995-10-01 | Pietroski et al. | Applicant |
| US5465717(A) | 1995-11-01 | Imran et al. | Applicant |
| US5476498(A) | 1995-12-01 | Ayers | Applicant |
| US5486159(A) | 1996-01-01 | Mahurkar | Applicant |
| US5507725(A) | 1996-04-01 | Savage et al. | Applicant |
| US5524632(A) | 1996-06-01 | Stein et al. | Applicant |
| US5527358(A) | 1996-06-01 | Mehmanesh et al. | Applicant |
| US5531686(A) | 1996-07-01 | Lundquist et al. | Applicant |
| US5549655(A) | 1996-08-01 | Erickson | Applicant |
| US5555618(A) | 1996-09-01 | Winkler | Applicant |
| US5567724(A) | 1996-10-01 | Kelleher et al. | Applicant |
| US5584873(A) | 1996-12-01 | Shoberg et al. | Applicant |
| US5604231(A) | 1997-02-01 | Smith et al. | Applicant |
| US5665103(A) | 1997-09-01 | Lafontaine et al. | Applicant |
| US5678535(A) | 1997-10-01 | Dimarco | Applicant |
| US5683370(A) | 1997-11-01 | Luther et al. | Applicant |
| US5709853(A) | 1998-01-01 | Iino et al. | Applicant |
| US5716392(A) | 1998-02-01 | Bourgeois et al. | Applicant |
| US5733255(A) | 1998-03-01 | Dinh et al. | Applicant |
| US5755765(A) | 1998-05-01 | Hyde et al. | Applicant |
| US5776111(A) | 1998-07-01 | Tesio | Applicant |
| US5779732(A) | 1998-07-01 | Amundson | Applicant |
| US5782828(A) | 1998-07-01 | Chen et al. | Applicant |
| US5785706(A) | 1998-07-01 | Bednarek | Applicant |
| US5788681(A) | 1998-08-01 | Weaver et al. | Applicant |
| US5813399(A) | 1998-09-01 | Isaza et al. | Applicant |
| US5814086(A) | 1998-09-01 | Hirschberg et al. | Applicant |
| USRE35924(E) | 1998-10-01 | Winkler | Applicant |
| US5824027(A) | 1998-10-01 | Hoffer et al. | Applicant |
| US5827192(A) | 1998-10-01 | Gopakumaran et al. | Applicant |
| US5916163(A) | 1999-06-01 | Panescu et al. | Applicant |
| US5944022(A) | 1999-08-01 | Nardella et al. | Applicant |
| US5954761(A) | 1999-09-01 | Machek et al. | Applicant |
| US5967978(A) | 1999-10-01 | Littmann et al. | Applicant |
| US5971933(A) | 1999-10-01 | Gopakumaran et al. | Applicant |
| US5983126(A) | 1999-11-01 | Wittkampf | Applicant |
| US6006134(A) | 1999-12-01 | Hill et al. | Applicant |
| US6024702(A) | 2000-02-01 | Iversen | Applicant |
| US6096728(A) | 2000-08-01 | Collins et al. | Applicant |
| US6120476(A) | 2000-09-01 | Fung et al. | Applicant |
| US6123699(A) | 2000-09-01 | Webster, Jr. | Applicant |
| US6126649(A) | 2000-10-01 | Vantassel et al. | Applicant |
| US6136021(A) | 2000-10-01 | Tockman et al. | Applicant |
| US6157862(A) | 2000-12-01 | Brownlee et al. | Applicant |
| US6161029(A) | 2000-12-01 | Spreigl et al. | Applicant |
| US6166048(A) | 2000-12-01 | Bencherif | Applicant |
| US6171277(B1) | 2001-01-01 | Ponzi | Applicant |
| US6183463(B1) | 2001-02-01 | Webster, Jr. | Applicant |
| US6198970(B1) | 2001-03-01 | Freed et al. | Applicant |
| US6198974(B1) | 2001-03-01 | Webster, Jr. | Applicant |
| US6201994(B1) | 2001-03-01 | Warman et al. | Applicant |
| US6208881(B1) | 2001-03-01 | Champeau | Applicant |
| US6210339(B1) | 2001-04-01 | Kiepen et al. | Applicant |
| US6212435(B1) | 2001-04-01 | Lattner et al. | Applicant |
| US6216045(B1) | 2001-04-01 | Black et al. | Applicant |
| US6236892(B1) | 2001-05-01 | Feler | Applicant |
| US6240320(B1) | 2001-05-01 | Spehr et al. | Applicant |
| US6249708(B1) | 2001-06-01 | Nelson | Examiner |
| US6251126(B1) | 2001-06-01 | Ottenhoff et al. | Applicant |
| US6269269(B1) | 2001-07-01 | Ottenhoff et al. | Applicant |
| US6292695(B1) | 2001-09-01 | Webster, Jr. et al. | Applicant |
| US6295475(B1) | 2001-09-01 | Morgan | Applicant |
| US6360740(B1) | 2002-03-01 | Ward et al. | Applicant |
| US6397108(B1) | 2002-05-01 | Camps et al. | Applicant |
| US6400976(B1) | 2002-06-01 | Champeau | Applicant |
| US6415183(B1) | 2002-07-01 | Scheiner et al. | Applicant |
| US6415187(B1) | 2002-07-01 | Kuzma et al. | Applicant |
| US6438427(B1) | 2002-08-01 | Rexhausen et al. | Applicant |
| US6445953(B1) | 2002-09-01 | Bulkes et al. | Applicant |
| US6449507(B1) | 2002-09-01 | Hill et al. | Applicant |
| US6463327(B1) | 2002-10-01 | Lurie et al. | Applicant |
| US6493590(B1) | 2002-12-01 | Wessman et al. | Applicant |
| US6508802(B1) | 2003-01-01 | Rosengart et al. | Applicant |
| US6526321(B1) | 2003-02-01 | Spehr | Applicant |
| US6569114(B2) | 2003-05-01 | Ponzi et al. | Applicant |
| US6584362(B1) | 2003-06-01 | Scheiner et al. | Applicant |
| US6585718(B2) | 2003-07-01 | Hayzelden et al. | Applicant |
| US6587726(B2) | 2003-07-01 | Lurie et al. | Applicant |
| US6602242(B1) | 2003-08-01 | Fung et al. | Applicant |
| US6610713(B2) | 2003-08-01 | Tracey | Applicant |
| US6630611(B1) | 2003-10-01 | Malowaniec | Applicant |
| US6643552(B2) | 2003-11-01 | Edell et al. | Applicant |
| US6651652(B1) | 2003-11-01 | Waard | Applicant |
| US6682526(B1) | 2004-01-01 | Jones et al. | Applicant |
| US6702780(B1) | 2004-03-01 | Gilboa et al. | Applicant |
| US6718208(B2) | 2004-04-01 | Hill et al. | Applicant |
| US6721603(B2) | 2004-04-01 | Zabara et al. | Applicant |
| US6757970(B1) | 2004-07-01 | Kuzma et al. | Applicant |
| US6778854(B2) | 2004-08-01 | Puskas | Applicant |
| US6779257(B2) | 2004-08-01 | Kiepen et al. | Applicant |
| US6844713(B2) | 2005-01-01 | Steber et al. | Applicant |
| USRE38705(E) | 2005-02-01 | Hill et al. | Applicant |
| US6881211(B2) | 2005-04-01 | Schweikert et al. | Applicant |
| US6885888(B2) | 2005-04-01 | Rezai | Applicant |
| US6907285(B2) | 2005-06-01 | Denker et al. | Applicant |
| US6934583(B2) | 2005-08-01 | Weinberg et al. | Applicant |
| US6981314(B2) | 2006-01-01 | Black et al. | Applicant |
| US6999820(B2) | 2006-02-01 | Jordan | Applicant |
| US7018374(B2) | 2006-03-01 | Schon et al. | Applicant |
| US7047627(B2) | 2006-05-01 | Black et al. | Applicant |
| US7071194(B2) | 2006-07-01 | Teng | Applicant |
| US7072720(B2) | 2006-07-01 | Puskas | Applicant |
| US7077823(B2) | 2006-07-01 | McDaniel | Applicant |
| US7082331(B1) | 2006-07-01 | Park et al. | Applicant |
| US7130700(B2) | 2006-10-01 | Gardeski | Examiner |
| US7142903(B2) | 2006-11-01 | Rodriguez et al. | Applicant |
| US7149585(B2) | 2006-12-01 | Wessman et al. | Applicant |
| US7155278(B2) | 2006-12-01 | King et al. | Applicant |
| US7168429(B2) | 2007-01-01 | Matthews et al. | Applicant |
| US7184829(B2) | 2007-02-01 | Hill et al. | Applicant |
| US7206636(B1) | 2007-04-01 | Turcott | Applicant |
| US7212867(B2) | 2007-05-01 | Van Venrooij et al. | Applicant |
| US7225016(B1) | 2007-05-01 | Koh | Applicant |
| US7225019(B2) | 2007-05-01 | Jahns et al. | Applicant |
| US7229429(B2) | 2007-06-01 | Martin et al. | Applicant |
| US7231260(B2) | 2007-06-01 | Wallace et al. | Applicant |
| US7235070(B2) | 2007-06-01 | Vanney | Applicant |
| US7269459(B1) | 2007-09-01 | Koh | Applicant |
| US7277757(B2) | 2007-10-01 | Casavant et al. | Applicant |
| US7283875(B2) | 2007-10-01 | Larsson et al. | Applicant |
| US7340302(B1) | 2008-03-01 | Falkenberg et al. | Applicant |
| US7363085(B1) | 2008-04-01 | Benser et al. | Applicant |
| US7363086(B1) | 2008-04-01 | Koh et al. | Applicant |
| US7371220(B1) | 2008-05-01 | Koh et al. | Applicant |
| US7416552(B2) | 2008-08-01 | Paul et al. | Applicant |
| US7421296(B1) | 2008-09-01 | Benser et al. | Applicant |
| US7454244(B2) | 2008-11-01 | Kassab et al. | Applicant |
| US7519425(B2) | 2009-04-01 | Benser et al. | Applicant |
| US7519426(B1) | 2009-04-01 | Koh et al. | Applicant |
| US7522953(B2) | 2009-04-01 | Gharib et al. | Applicant |
| US7553305(B2) | 2009-06-01 | Honebrink et al. | Applicant |
| US7555349(B2) | 2009-06-01 | Wessman et al. | Applicant |
| US7569029(B2) | 2009-08-01 | Clark et al. | Applicant |
| US7591265(B2) | 2009-09-01 | Lee et al. | Applicant |
| US7593760(B2) | 2009-09-01 | Rodriguez et al. | Applicant |
| US7613524(B2) | 2009-11-01 | Jordan | Applicant |
| US7636600(B1) | 2009-12-01 | Koh | Applicant |
| US7670284(B2) | 2010-03-01 | Padget et al. | Applicant |
| US7672728(B2) | 2010-03-01 | Libbus et al. | Applicant |
| US7672729(B2) | 2010-03-01 | Koh et al. | Applicant |
| US7676275(B1) | 2010-03-01 | Farazi et al. | Applicant |
| US7676910(B2) | 2010-03-01 | Kiepen et al. | Applicant |
| US7697984(B2) | 2010-04-01 | Hill et al. | Applicant |
| US7747323(B2) | 2010-06-01 | Libbus et al. | Applicant |
| US7771388(B2) | 2010-08-01 | Olsen et al. | Applicant |
| US7783362(B2) | 2010-08-01 | Whitehurst et al. | Applicant |
| US7794407(B2) | 2010-09-01 | Rothenberg | Applicant |
| US7797050(B2) | 2010-09-01 | Libbus et al. | Applicant |
| US7813805(B1) | 2010-10-01 | Farazi | Applicant |
| US7819883(B2) | 2010-10-01 | Westlund et al. | Applicant |
| US7840270(B2) | 2010-11-01 | Ignagni et al. | Applicant |
| US7853302(B2) | 2010-12-01 | Rodriguez et al. | Applicant |
| US7869865(B2) | 2011-01-01 | Govari et al. | Applicant |
| US7891085(B1) | 2011-02-01 | Kuzma et al. | Applicant |
| US7925352(B2) | 2011-04-01 | Stack et al. | Applicant |
| US7949409(B2) | 2011-05-01 | Bly et al. | Applicant |
| US7949412(B1) | 2011-05-01 | Harrison et al. | Applicant |
| US7962215(B2) | 2011-06-01 | Ignagni et al. | Applicant |
| US7970475(B2) | 2011-06-01 | Tehrani et al. | Applicant |
| US7972323(B1) | 2011-07-01 | Bencini et al. | Applicant |
| US7974693(B2) | 2011-07-01 | David et al. | Applicant |
| US7974705(B2) | 2011-07-01 | Zdeblick et al. | Applicant |
| US7979128(B2) | 2011-07-01 | Tehrani et al. | Applicant |
| US7994655(B2) | 2011-08-01 | Bauer et al. | Applicant |
| US8000765(B2) | 2011-08-01 | Rodriguez et al. | Applicant |
| US8019439(B2) | 2011-09-01 | Kuzma et al. | Applicant |
| US8021327(B2) | 2011-09-01 | Selkee | Applicant |
| US8036750(B2) | 2011-10-01 | Caparso et al. | Applicant |
| US8050765(B2) | 2011-11-01 | Lee et al. | Applicant |
| US8052607(B2) | 2011-11-01 | Byrd | Applicant |
| US8104470(B2) | 2012-01-01 | Lee et al. | Applicant |
| US8116872(B2) | 2012-02-01 | Tehrani et al. | Applicant |
| US8121692(B2) | 2012-02-01 | Haefner et al. | Applicant |
| US8135471(B2) | 2012-03-01 | Zhang et al. | Applicant |
| US8140164(B2) | 2012-03-01 | Tehrani et al. | Applicant |
| US8147486(B2) | 2012-04-01 | Honour et al. | Applicant |
| US8160701(B2) | 2012-04-01 | Zhao et al. | Applicant |
| US8160711(B2) | 2012-04-01 | Tehrani et al. | Applicant |
| US8195297(B2) | 2012-06-01 | Penner | Applicant |
| US8200336(B2) | 2012-06-01 | Tehrani et al. | Applicant |
| US8206343(B2) | 2012-06-01 | Racz | Applicant |
| US8224456(B2) | 2012-07-01 | Daglow et al. | Applicant |
| US8233987(B2) | 2012-07-01 | Gelfand et al. | Applicant |
| US8233993(B2) | 2012-07-01 | Jordan | Applicant |
| US8239037(B2) | 2012-08-01 | Glenn et al. | Applicant |
| US8244358(B2) | 2012-08-01 | Tehrani et al. | Applicant |
| US8244359(B2) | 2012-08-01 | Gelfand et al. | Applicant |
| US8244378(B2) | 2012-08-01 | Bly et al. | Applicant |
| US8255056(B2) | 2012-08-01 | Tehrani | Applicant |
| US8256419(B2) | 2012-09-01 | Sinderby et al. | Applicant |
| US8265736(B2) | 2012-09-01 | Sathaye et al. | Applicant |
| US8265759(B2) | 2012-09-01 | Tehrani et al. | Applicant |
| US8275440(B2) | 2012-09-01 | Rodriguez et al. | Applicant |
| US8280513(B2) | 2012-10-01 | Tehrani et al. | Applicant |
| US8315713(B2) | 2012-11-01 | Burnes et al. | Applicant |
| US8321808(B2) | 2012-11-01 | Goetz et al. | Applicant |
| US8335567(B2) | 2012-12-01 | Tehrani et al. | Applicant |
| US8340783(B2) | 2012-12-01 | Sommer et al. | Applicant |
| US8348941(B2) | 2013-01-01 | Tehrani | Applicant |
| US8369954(B2) | 2013-02-01 | Stack et al. | Applicant |
| US8374704(B2) | 2013-02-01 | Desai et al. | Applicant |
| US8388541(B2) | 2013-03-01 | Messerly et al. | Applicant |
| US8388546(B2) | 2013-03-01 | Rothenberg | Applicant |
| US8391956(B2) | 2013-03-01 | Zellers et al. | Applicant |
| US8401640(B2) | 2013-03-01 | Zhao et al. | Applicant |
| US8401651(B2) | 2013-03-01 | Caparso et al. | Applicant |
| US8406883(B1) | 2013-03-01 | Barker | Applicant |
| US8406885(B2) | 2013-03-01 | Ignagni et al. | Applicant |
| US8412331(B2) | 2013-04-01 | Tehrani et al. | Applicant |
| US8412350(B2) | 2013-04-01 | Bly | Applicant |
| US8428711(B2) | 2013-04-01 | Lin et al. | Applicant |
| US8428726(B2) | 2013-04-01 | Ignagni et al. | Applicant |
| US8428730(B2) | 2013-04-01 | Stack et al. | Applicant |
| US8433412(B1) | 2013-04-01 | Westlund et al. | Applicant |
| US8442638(B2) | 2013-05-01 | Libbus et al. | Applicant |
| US8457764(B2) | 2013-06-01 | Ramachandran et al. | Applicant |
| US8467876(B2) | 2013-06-01 | Tehrani | Applicant |
| US8473068(B2) | 2013-06-01 | Farazi | Applicant |
| US8478412(B2) | 2013-07-01 | Ignagni et al. | Applicant |
| US8478413(B2) | 2013-07-01 | Karamanoglu et al. | Applicant |
| US8478426(B2) | 2013-07-01 | Barker | Applicant |
| US8483834(B2) | 2013-07-01 | Lee et al. | Applicant |
| US8504158(B2) | 2013-08-01 | Karamanoglu et al. | Applicant |
| US8504161(B1) | 2013-08-01 | Kornet et al. | Applicant |
| US8509901(B2) | 2013-08-01 | Tehrani | Applicant |
| US8509902(B2) | 2013-08-01 | Cho et al. | Applicant |
| US8509919(B2) | 2013-08-01 | Yoo et al. | Applicant |
| US8512256(B2) | 2013-08-01 | Rothenberg | Applicant |
| US8522779(B2) | 2013-09-01 | Lee et al. | Applicant |
| US8527036(B2) | 2013-09-01 | Jalde et al. | Applicant |
| US8532793(B2) | 2013-09-01 | Morris et al. | Applicant |
| US8554323(B2) | 2013-10-01 | Haefner et al. | Applicant |
| US8560072(B2) | 2013-10-01 | Caparso et al. | Applicant |
| US8560086(B2) | 2013-10-01 | Just et al. | Applicant |
| US8571662(B2) | 2013-10-01 | Hoffer | Applicant |
| US8571685(B2) | 2013-10-01 | Daglow et al. | Applicant |
| US8615297(B2) | 2013-12-01 | Sathaye et al. | Applicant |
| US8617228(B2) | 2013-12-01 | Wittenberger et al. | Applicant |
| US8620412(B2) | 2013-12-01 | Griffiths et al. | Applicant |
| US8620450(B2) | 2013-12-01 | Tockman et al. | Applicant |
| US8626292(B2) | 2014-01-01 | McCabe et al. | Applicant |
| US8630707(B2) | 2014-01-01 | Zhao et al. | Applicant |
| US8644939(B2) | 2014-02-01 | Wilson et al. | Applicant |
| US8644952(B2) | 2014-02-01 | Desai et al. | Applicant |
| US8646172(B2) | 2014-02-01 | Kuzma et al. | Applicant |
| US8650747(B2) | 2014-02-01 | Kuzma et al. | Applicant |
| US8676323(B2) | 2014-03-01 | Ignagni et al. | Applicant |
| US8676344(B2) | 2014-03-01 | Desai et al. | Applicant |
| US8694123(B2) | 2014-04-01 | Wahlstrand et al. | Applicant |
| US8696656(B2) | 2014-04-01 | Abboud et al. | Applicant |
| US8706223(B2) | 2014-04-01 | Zhou et al. | Applicant |
| US8706235(B2) | 2014-04-01 | Karamanoglu et al. | Applicant |
| US8706236(B2) | 2014-04-01 | Ignagni et al. | Applicant |
| US8718763(B2) | 2014-05-01 | Zhou et al. | Applicant |
| US8725259(B2) | 2014-05-01 | Kornet et al. | Applicant |
| US8738154(B2) | 2014-05-01 | Zdeblick et al. | Applicant |
| US8755889(B2) | 2014-06-01 | Scheiner | Applicant |
| US8774907(B2) | 2014-07-01 | Rothenberg | Applicant |
| US8781578(B2) | 2014-07-01 | McCabe et al. | Applicant |
| US8781582(B2) | 2014-07-01 | Ziegler et al. | Applicant |
| US8781583(B2) | 2014-07-01 | Cornelussen et al. | Applicant |
| US8801693(B2) | 2014-08-01 | He et al. | Applicant |
| US8805511(B2) | 2014-08-01 | Karamanoglu et al. | Applicant |
| US8838245(B2) | 2014-09-01 | Lin et al. | Applicant |
| US8858455(B2) | 2014-10-01 | Rothenberg | Applicant |
| US8863742(B2) | 2014-10-01 | Blomquist et al. | Applicant |
| US8886277(B2) | 2014-11-01 | Kim et al. | Applicant |
| US8897879(B2) | 2014-11-01 | Karamanoglu et al. | Applicant |
| US8903507(B2) | 2014-12-01 | Desai et al. | Applicant |
| US8903509(B2) | 2014-12-01 | Tockman et al. | Applicant |
| US8909341(B2) | 2014-12-01 | Gelfand et al. | Applicant |
| US8914113(B2) | 2014-12-01 | Zhang et al. | Applicant |
| US8918169(B2) | 2014-12-01 | Kassab et al. | Applicant |
| US8918987(B2) | 2014-12-01 | Kuzma et al. | Applicant |
| US8923971(B2) | 2014-12-01 | Haefner et al. | Applicant |
| US8942823(B2) | 2015-01-01 | Desai et al. | Applicant |
| US8942824(B2) | 2015-01-01 | Yoo et al. | Applicant |
| US8948884(B2) | 2015-02-01 | Ramachandran et al. | Applicant |
| US8968299(B2) | 2015-03-01 | Kauphusman et al. | Applicant |
| US8972015(B2) | 2015-03-01 | Stack et al. | Applicant |
| US8983602(B2) | 2015-03-01 | Sathaye et al. | Applicant |
| US9008775(B2) | 2015-04-01 | Sathaye et al. | Applicant |
| US9026231(B2) | 2015-05-01 | Hoffer | Applicant |
| US9037264(B2) | 2015-05-01 | Just et al. | Applicant |
| US9042981(B2) | 2015-05-01 | Yoo et al. | Applicant |
| US9072864(B2) | 2015-07-01 | Putz | Applicant |
| US9072899(B1) | 2015-07-01 | Nickloes | Applicant |
| US9108058(B2) | 2015-08-01 | Hoffer | Applicant |
| US9108059(B2) | 2015-08-01 | Hoffer | Applicant |
| US9125578(B2) | 2015-09-01 | Grunwald | Applicant |
| US9138580(B2) | 2015-09-01 | Ignagni et al. | Applicant |
| US9138585(B2) | 2015-09-01 | Saha et al. | Applicant |
| US9149642(B2) | 2015-10-01 | McCabe et al. | Applicant |
| US9168377(B2) | 2015-10-01 | Hoffer | Applicant |
| US9205258(B2) | 2015-12-01 | Simon et al. | Applicant |
| US9216291(B2) | 2015-12-01 | Lee et al. | Applicant |
| US9220898(B2) | 2015-12-01 | Hoffer | Applicant |
| US9226688(B2) | 2016-01-01 | Jacobsen et al. | Applicant |
| US9226689(B2) | 2016-01-01 | Jacobsen et al. | Applicant |
| US9242088(B2) | 2016-01-01 | Thakkar et al. | Applicant |
| US9259573(B2) | 2016-02-01 | Tehrani et al. | Applicant |
| US9295846(B2) | 2016-03-01 | Westlund et al. | Applicant |
| US9314618(B2) | 2016-04-01 | Imran et al. | Applicant |
| US9333363(B2) | 2016-05-01 | Hoffer et al. | Applicant |
| US9345422(B2) | 2016-05-01 | Rothenberg | Applicant |
| US9370657(B2) | 2016-06-01 | Tehrani et al. | Applicant |
| US9398931(B2) | 2016-07-01 | Wittenberger et al. | Applicant |
| US9415188(B2) | 2016-08-01 | He et al. | Applicant |
| US9427566(B2) | 2016-08-01 | Reed et al. | Applicant |
| US9427588(B2) | 2016-08-01 | Sathaye et al. | Applicant |
| US9474894(B2) | 2016-10-01 | Mercanzini et al. | Applicant |
| US9485873(B2) | 2016-11-01 | Shah et al. | Applicant |
| US9498625(B2) | 2016-11-01 | Bauer et al. | Applicant |
| US9498631(B2) | 2016-11-01 | Demmer et al. | Applicant |
| US9504837(B2) | 2016-11-01 | Demmer et al. | Applicant |
| US9532724(B2) | 2017-01-01 | Grunwald et al. | Applicant |
| US9533160(B2) | 2017-01-01 | Brooke et al. | Applicant |
| US9539429(B2) | 2017-01-01 | Brooke et al. | Applicant |
| US9545511(B2) | 2017-01-01 | Thakkar et al. | Applicant |
| US9561369(B2) | 2017-02-01 | Burnes et al. | Applicant |
| US9566436(B2) | 2017-02-01 | Hoffer et al. | Applicant |
| US9572982(B2) | 2017-02-01 | Burnes et al. | Applicant |
| US9597509(B2) | 2017-03-01 | Hoffer et al. | Applicant |
| US9615759(B2) | 2017-04-01 | Hurezan et al. | Applicant |
| US9623252(B2) | 2017-04-01 | Sathaye et al. | Applicant |
| US9662494(B2) | 2017-05-01 | Young et al. | Applicant |
| US9682235(B1) | 2017-06-01 | O'Mahony et al. | Applicant |
| US9694185(B2) | 2017-07-01 | Bauer | Applicant |
| US9717899(B2) | 2017-08-01 | Kuzma et al. | Applicant |
| US9724018(B2) | 2017-08-01 | Cho et al. | Applicant |
| US9744351(B1) | 2017-08-01 | Gelfand et al. | Applicant |
| US9776005(B2) | 2017-10-01 | Meyyappan et al. | Applicant |
| US9861817(B2) | 2018-01-01 | Cho et al. | Applicant |
| US9872989(B2) | 2018-01-01 | Jung et al. | Applicant |
| US9884178(B2) | 2018-02-01 | Bouton et al. | Applicant |
| US9884179(B2) | 2018-02-01 | Bouton et al. | Applicant |
| US9919149(B2) | 2018-03-01 | Imran et al. | Applicant |
| US9931504(B2) | 2018-04-01 | Thakkar et al. | Applicant |
| US9950167(B2) | 2018-04-01 | Hoffer et al. | Applicant |
| US9956396(B2) | 2018-05-01 | Young et al. | Applicant |
| US9968785(B2) | 2018-05-01 | Hoffer et al. | Applicant |
| US9968786(B2) | 2018-05-01 | Bauer et al. | Applicant |
| US2001/0052345(A1) | 2001-12-01 | Niazi | Applicant |
| US2002/0026228(A1) | 2002-02-01 | Schauerte | Applicant |
| US2002/0056454(A1) | 2002-05-01 | Samzelius | Applicant |
| US2002/0065544(A1) | 2002-05-01 | Smits et al. | Applicant |
| US2002/0087156(A1) | 2002-07-01 | Maguire et al. | Applicant |
| US2002/0128546(A1) | 2002-09-01 | Silver | Applicant |
| US2002/0188325(A1) | 2002-12-01 | Hill et al. | Applicant |
| US2003/0078623(A1) | 2003-04-01 | Weinberg et al. | Applicant |
| US2003/0195571(A1) | 2003-10-01 | Burnes et al. | Applicant |
| US2004/0003813(A1) | 2004-01-01 | Banner et al. | Applicant |
| US2004/0010303(A1) | 2004-01-01 | Bolea et al. | Applicant |
| US2004/0030362(A1) | 2004-02-01 | Hill et al. | Applicant |
| US2004/0044377(A1) | 2004-03-01 | Larsson et al. | Applicant |
| US2004/0064069(A1) | 2004-04-01 | Reynolds et al. | Applicant |
| US2004/0077936(A1) | 2004-04-01 | Larsson et al. | Applicant |
| US2004/0088015(A1) | 2004-05-01 | Casavant et al. | Applicant |
| US2004/0111139(A1) | 2004-06-01 | McCreery | Applicant |
| US2004/0186543(A1) | 2004-09-01 | King et al. | Applicant |
| US2004/0210261(A1) | 2004-10-01 | King et al. | Applicant |
| US2005/0004565(A1) | 2005-01-01 | Vanney | Applicant |
| US2005/0013879(A1) | 2005-01-01 | Lin et al. | Applicant |
| US2005/0021102(A1) | 2005-01-01 | Ignagni et al. | Applicant |
| US2005/0027338(A1) | 2005-02-01 | Hill | Applicant |
| US2005/0033136(A1) | 2005-02-01 | Govari et al. | Applicant |
| US2005/0033137(A1) | 2005-02-01 | Oral et al. | Applicant |
| US2005/0043765(A1) | 2005-02-01 | Williams et al. | Applicant |
| US2005/0065567(A1) | 2005-03-01 | Lee et al. | Applicant |
| US2005/0070981(A1) | 2005-03-01 | Verma | Applicant |
| US2005/0075578(A1) | 2005-04-01 | Gharib et al. | Applicant |
| US2005/0085865(A1) | 2005-04-01 | Tehrani | Applicant |
| US2005/0085866(A1) | 2005-04-01 | Tehrani | Applicant |
| US2005/0085867(A1) | 2005-04-01 | Tehrani et al. | Applicant |
| US2005/0085868(A1) | 2005-04-01 | Tehrani et al. | Applicant |
| US2005/0085869(A1) | 2005-04-01 | Tehrani et al. | Applicant |
| US2005/0096710(A1) | 2005-05-01 | Kieval | Applicant |
| US2005/0109340(A1) | 2005-05-01 | Tehrani | Applicant |
| US2005/0113710(A1) | 2005-05-01 | Stahmann et al. | Applicant |
| US2005/0115561(A1) | 2005-06-01 | Stahmann et al. | Applicant |
| US2005/0131485(A1) | 2005-06-01 | Knudson et al. | Applicant |
| US2005/0138791(A1) | 2005-06-01 | Black et al. | Applicant |
| US2005/0138792(A1) | 2005-06-01 | Black et al. | Applicant |
| US2005/0143787(A1) | 2005-06-01 | Boveja et al. | Applicant |
| US2005/0165457(A1) | 2005-07-01 | Benser et al. | Applicant |
| US2005/0182454(A1) | 2005-08-01 | Gharib et al. | Applicant |
| US2005/0187584(A1) | 2005-08-01 | Denker et al. | Applicant |
| US2005/0192655(A1) | 2005-09-01 | Black et al. | Applicant |
| US2005/0251238(A1) | 2005-11-01 | Wallace et al. | Applicant |
| US2005/0251239(A1) | 2005-11-01 | Wallace et al. | Applicant |
| US2005/0288728(A1) | 2005-12-01 | Libbus et al. | Applicant |
| US2005/0288730(A1) | 2005-12-01 | Deem et al. | Applicant |
| US2006/0030894(A1) | 2006-02-01 | Tehrani | Applicant |
| US2006/0035849(A1) | 2006-02-01 | Spiegelman et al. | Applicant |
| US2006/0058852(A1) | 2006-03-01 | Koh et al. | Applicant |
| US2006/0074449(A1) | 2006-04-01 | Denker et al. | Applicant |
| US2006/0122661(A1) | 2006-06-01 | Mandell | Applicant |
| US2006/0122662(A1) | 2006-06-01 | Tehrani et al. | Applicant |
| US2006/0130833(A1) | 2006-06-01 | Younes | Applicant |
| US2006/0142815(A1) | 2006-06-01 | Tehrani et al. | Applicant |
| US2006/0149334(A1) | 2006-07-01 | Tehrani et al. | Applicant |
| US2006/0155222(A1) | 2006-07-01 | Sherman et al. | Applicant |
| US2006/0167523(A1) | 2006-07-01 | Tehrani et al. | Applicant |
| US2006/0188325(A1) | 2006-08-01 | Dolan | Applicant |
| US2006/0195159(A1) | 2006-08-01 | Bradley et al. | Applicant |
| US2006/0217791(A1) | 2006-09-01 | Spinka | Examiner |
| US2006/0224209(A1) | 2006-10-01 | Meyer | Applicant |
| US2006/0229677(A1) | 2006-10-01 | Moffitt et al. | Applicant |
| US2006/0247729(A1) | 2006-11-01 | Tehrani et al. | Applicant |
| US2006/0253161(A1) | 2006-11-01 | Libbus et al. | Applicant |
| US2006/0253182(A1) | 2006-11-01 | King | Applicant |
| US2006/0258667(A1) | 2006-11-01 | Teng | Applicant |
| US2006/0259107(A1) | 2006-11-01 | Caparso et al. | Applicant |
| US2006/0282131(A1) | 2006-12-01 | Caparso et al. | Applicant |
| US2006/0287679(A1) | 2006-12-01 | Stone | Applicant |
| US2007/0005053(A1) | 2007-01-01 | Dando | Applicant |
| US2007/0021795(A1) | 2007-01-01 | Tehrani | Applicant |
| US2007/0027448(A1) | 2007-02-01 | Paul | Examiner |
| US2007/0087314(A1) | 2007-04-01 | Gomo | Applicant |
| US2007/0093875(A1) | 2007-04-01 | Chavan et al. | Applicant |
| US2007/0106357(A1) | 2007-05-01 | Denker et al. | Applicant |
| US2007/0112402(A1) | 2007-05-01 | Grill et al. | Applicant |
| US2007/0112403(A1) | 2007-05-01 | Moffitt et al. | Applicant |
| US2007/0118183(A1) | 2007-05-01 | Gelfand et al. | Applicant |
| US2007/0150006(A1) | 2007-06-01 | Libbus et al. | Applicant |
| US2007/0168007(A1) | 2007-07-01 | Kuzma et al. | Applicant |
| US2007/0173900(A1) | 2007-07-01 | Siegel et al. | Applicant |
| US2007/0191908(A1) | 2007-08-01 | Jacob et al. | Applicant |
| US2007/0196780(A1) | 2007-08-01 | Ware et al. | Applicant |
| US2007/0203549(A1) | 2007-08-01 | Demarais et al. | Applicant |
| US2007/0208388(A1) | 2007-09-01 | Jahns et al. | Applicant |
| US2007/0221224(A1) | 2007-09-01 | Pittman et al. | Applicant |
| US2007/0240718(A1) | 2007-10-01 | Daly | Applicant |
| US2007/0250056(A1) | 2007-10-01 | Vanney | Applicant |
| US2007/0250162(A1) | 2007-10-01 | Royalty | Applicant |
| US2007/0255379(A1) | 2007-11-01 | Williams et al. | Applicant |
| US2007/0265611(A1) | 2007-11-01 | Ignagni et al. | Applicant |
| US2007/0288076(A1) | 2007-12-01 | Bulkes et al. | Applicant |
| US2008/0039916(A1) | 2008-02-01 | Colliou et al. | Applicant |
| US2008/0065002(A1) | 2008-03-01 | Lobl et al. | Applicant |
| US2008/0125828(A1) | 2008-05-01 | Ignagni et al. | Applicant |
| US2008/0161878(A1) | 2008-07-01 | Tehrani et al. | Applicant |
| US2008/0167695(A1) | 2008-07-01 | Tehrani et al. | Applicant |
| US2008/0177347(A1) | 2008-07-01 | Tehrani et al. | Applicant |
| US2008/0183186(A1) | 2008-07-01 | Bly et al. | Applicant |
| US2008/0183187(A1) | 2008-07-01 | Bly | Applicant |
| US2008/0183239(A1) | 2008-07-01 | Tehrani et al. | Applicant |
| US2008/0183240(A1) | 2008-07-01 | Tehrani et al. | Applicant |
| US2008/0183253(A1) | 2008-07-01 | Bly | Applicant |
| US2008/0183254(A1) | 2008-07-01 | Bly et al. | Applicant |
| US2008/0183255(A1) | 2008-07-01 | Bly et al. | Applicant |
| US2008/0183259(A1) | 2008-07-01 | Bly et al. | Applicant |
| US2008/0183264(A1) | 2008-07-01 | Bly et al. | Applicant |
| US2008/0183265(A1) | 2008-07-01 | Bly et al. | Applicant |
| US2008/0188903(A1) | 2008-08-01 | Tehrani et al. | Applicant |
| US2008/0215106(A1) | 2008-09-01 | Lee et al. | Applicant |
| US2008/0288010(A1) | 2008-11-01 | Tehrani et al. | Applicant |
| US2008/0288015(A1) | 2008-11-01 | Tehrani et al. | Applicant |
| US2008/0312712(A1) | 2008-12-01 | Penner | Applicant |
| US2008/0312725(A1) | 2008-12-01 | Penner | Applicant |
| US2009/0024047(A1) | 2009-01-01 | Shipley et al. | Applicant |
| US2009/0036947(A1) | 2009-02-01 | Westlund et al. | Applicant |
| US2009/0118785(A1) | 2009-05-01 | Ignagni et al. | Applicant |
| US2009/0248122(A1) | 2009-10-01 | Pianca | Examiner |
| US2009/0275956(A1) | 2009-11-01 | Burnes et al. | Applicant |
| US2009/0275996(A1) | 2009-11-01 | Burnes et al. | Applicant |
| US2009/0276022(A1) | 2009-11-01 | Burnes et al. | Applicant |
| US2010/0022950(A1) | 2010-01-01 | Anderson et al. | Applicant |
| US2010/0036451(A1) | 2010-02-01 | Hoffer | Examiner |
| US2010/0077606(A1) | 2010-04-01 | Black et al. | Applicant |
| US2010/0094376(A1) | 2010-04-01 | Penner | Applicant |
| US2010/0114227(A1) | 2010-05-01 | Cholette | Applicant |
| US2010/0114254(A1) | 2010-05-01 | Kornet | Applicant |
| US2010/0198296(A1) | 2010-08-01 | Ignagni et al. | Applicant |
| US2010/0204766(A1) | 2010-08-01 | Zdeblick et al. | Applicant |
| US2010/0268311(A1) | 2010-10-01 | Cardinal et al. | Applicant |
| US2010/0319691(A1) | 2010-12-01 | Lurie et al. | Applicant |
| US2011/0060381(A1) | 2011-03-01 | Ignagni et al. | Applicant |
| US2011/0077726(A1) | 2011-03-01 | Westlund et al. | Applicant |
| US2011/0118815(A1) | 2011-05-01 | Kuzma et al. | Applicant |
| US2011/0230932(A1) | 2011-09-01 | Tehrani et al. | Applicant |
| US2011/0230935(A1) | 2011-09-01 | Zdeblick | Applicant |
| US2011/0230945(A1) | 2011-09-01 | Ohtaka et al. | Applicant |
| US2011/0270358(A1) | 2011-11-01 | Davis et al. | Applicant |
| US2011/0288609(A1) | 2011-11-01 | Tehrani et al. | Applicant |
| US2012/0035684(A1) | 2012-02-01 | Thompson et al. | Applicant |
| US2012/0053654(A1) | 2012-03-01 | Tehrani et al. | Applicant |
| US2012/0078320(A1) | 2012-03-01 | Schotzko et al. | Applicant |
| US2012/0130217(A1) | 2012-05-01 | Kauphusman et al. | Applicant |
| US2012/0158091(A1) | 2012-06-01 | Tehrani et al. | Applicant |
| US2012/0209284(A1) | 2012-08-01 | Westlund et al. | Applicant |
| US2012/0215278(A1) | 2012-08-01 | Penner | Applicant |
| US2012/0323293(A1) | 2012-12-01 | Tehrani et al. | Applicant |
| US2013/0018247(A1) | 2013-01-01 | Glenn et al. | Applicant |
| US2013/0018427(A1) | 2013-01-01 | Pham et al. | Applicant |
| US2013/0023972(A1) | 2013-01-01 | Kuzma et al. | Applicant |
| US2013/0030496(A1) | 2013-01-01 | Karamanoglu et al. | Applicant |
| US2013/0030497(A1) | 2013-01-01 | Karamanoglu et al. | Applicant |
| US2013/0030498(A1) | 2013-01-01 | Karamanoglu et al. | Applicant |
| US2013/0060245(A1) | 2013-03-01 | Grunewald et al. | Applicant |
| US2013/0116743(A1) | 2013-05-01 | Karamanoglu et al. | Applicant |
| US2013/0123891(A1) | 2013-05-01 | Swanson | Applicant |
| US2013/0131743(A1) | 2013-05-01 | Yamasaki et al. | Applicant |
| US2013/0158625(A1) | 2013-06-01 | Gelfand et al. | Applicant |
| US2013/0165989(A1) | 2013-06-01 | Gelfand et al. | Applicant |
| US2013/0167372(A1) | 2013-07-01 | Black et al. | Applicant |
| US2013/0197601(A1) | 2013-08-01 | Tehrani et al. | Applicant |
| US2013/0237906(A1) | 2013-09-01 | Park et al. | Applicant |
| US2013/0268018(A1) | 2013-10-01 | Brooke et al. | Applicant |
| US2013/0289686(A1) | 2013-10-01 | Masson et al. | Applicant |
| US2013/0296964(A1) | 2013-11-01 | Tehrani | Applicant |
| US2013/0296973(A1) | 2013-11-01 | Tehrani et al. | Applicant |
| US2013/0317587(A1) | 2013-11-01 | Barker | Applicant |
| US2013/0333696(A1) | 2013-12-01 | Lee et al. | Applicant |
| US2014/0067032(A1) | 2014-03-01 | Morris et al. | Applicant |
| US2014/0088580(A1) | 2014-03-01 | Wittenberger et al. | Applicant |
| US2014/0114371(A1) | 2014-04-01 | Westlund et al. | Applicant |
| US2014/0121716(A1) | 2014-05-01 | Casavant et al. | Applicant |
| US2014/0128953(A1) | 2014-05-01 | Zhao et al. | Applicant |
| US2014/0148780(A1) | 2014-05-01 | Putz | Applicant |
| US2014/0316486(A1) | 2014-10-01 | Zhou et al. | Applicant |
| US2014/0324115(A1) | 2014-10-01 | Ziegler et al. | Applicant |
| US2014/0378803(A1) | 2014-12-01 | Geistert et al. | Applicant |
| US2015/0018839(A1) | 2015-01-01 | Morris et al. | Applicant |
| US2015/0034081(A1) | 2015-02-01 | Tehrani et al. | Applicant |
| US2015/0045810(A1) | 2015-02-01 | Hoffer et al. | Applicant |
| US2015/0045848(A1) | 2015-02-01 | Cho et al. | Applicant |
| US2015/0119950(A1) | 2015-04-01 | Demmer et al. | Applicant |
| US2015/0148877(A1) | 2015-05-01 | Thakkar | Examiner |
| US2015/0165207(A1) | 2015-06-01 | Karamanoglu | Applicant |
| US2015/0196354(A1) | 2015-07-01 | Haverkost et al. | Applicant |
| US2015/0196356(A1) | 2015-07-01 | Kauphusman et al. | Applicant |
| US2015/0231348(A1) | 2015-08-01 | Lee et al. | Applicant |
| US2015/0250982(A1) | 2015-09-01 | Osypka | Applicant |
| US2015/0265833(A1) | 2015-09-01 | Meyyappan et al. | Applicant |
| US2015/0283340(A1) | 2015-10-01 | Zhang et al. | Applicant |
| US2015/0290476(A1) | 2015-10-01 | Krocak et al. | Applicant |
| US2015/0359487(A1) | 2015-12-01 | Coulombe | Applicant |
| US2015/0374252(A1) | 2015-12-01 | De La Rama et al. | Applicant |
| US2015/0374991(A1) | 2015-12-01 | Morris et al. | Applicant |
| US2016/0001072(A1) | 2016-01-01 | Gelfand et al. | Applicant |
| US2016/0101280(A1) | 2016-04-01 | Thakkar | Examiner |
| US2016/0144078(A1) | 2016-05-01 | Young et al. | Applicant |
| US2016/0193460(A1) | 2016-07-01 | Xu et al. | Applicant |
| US2016/0228696(A1) | 2016-08-01 | Imran et al. | Applicant |
| US2016/0239627(A1) | 2016-08-01 | Cerny et al. | Applicant |
| US2016/0256692(A1) | 2016-09-01 | Baru | Applicant |
| US2016/0310730(A1) | 2016-10-01 | Martins et al. | Applicant |
| US2016/0331326(A1) | 2016-11-01 | Xiang et al. | Applicant |
| US2016/0367815(A1) | 2016-12-01 | Hoffer | Applicant |
| US2017/0007825(A1) | 2017-01-01 | Thakkar et al. | Applicant |
| US2017/0013713(A1) | 2017-01-01 | Shah et al. | Applicant |
| US2017/0021166(A1) | 2017-01-01 | Bauer et al. | Applicant |
| US2017/0028191(A1) | 2017-02-01 | Mercanzini et al. | Applicant |
| US2017/0036017(A1) | 2017-02-01 | Tehrani et al. | Applicant |
| US2017/0050033(A1) | 2017-02-01 | Wechter | Applicant |
| US2017/0143973(A1) | 2017-05-01 | Tehrani | Applicant |
| US2017/0143975(A1) | 2017-05-01 | Hoffer et al. | Applicant |
| US2017/0196503(A1) | 2017-07-01 | Narayan et al. | Applicant |
| US2017/0224993(A1) | 2017-08-01 | Sathaye et al. | Applicant |
| US2017/0232250(A1) | 2017-08-01 | Kim et al. | Applicant |
| US2017/0252558(A1) | 2017-09-01 | O'Mahony et al. | Applicant |
| US2017/0291023(A1) | 2017-10-01 | Kuzma et al. | Applicant |
| US2017/0296812(A1) | 2017-10-01 | O'Mahony et al. | Applicant |
| US2017/0312006(A1) | 2017-11-01 | McFarlin et al. | Applicant |
| US2017/0312507(A1) | 2017-11-01 | Bauer et al. | Applicant |
| US2017/0312508(A1) | 2017-11-01 | Bauer et al. | Applicant |
| US2017/0312509(A1) | 2017-11-01 | Bauer et al. | Applicant |
| US2017/0326359(A1) | 2017-11-01 | Gelfand et al. | Applicant |
| US2017/0347921(A1) | 2017-12-01 | Haber et al. | Applicant |
| US2018/0001086(A1) | 2018-01-01 | Bartholomew et al. | Applicant |
| US2018/0008821(A1) | 2018-01-01 | Gonzalez et al. | Applicant |
| US2018/0110562(A1) | 2018-04-01 | Govari et al. | Applicant |
| US2018/0117334(A1) | 2018-05-01 | Jung | Applicant |
| CN1652839(A) | 2005-08-01 | Applicant | |
| CN102143781(A) | 2011-08-01 | Applicant | |
| EP993840(A1) | 2000-04-01 | Applicant | |
| EP1304135(A2) | 2003-04-01 | Applicant | |
| EP605796(B1) | 2003-08-01 | Applicant | |
| EP2489395(A1) | 2012-08-01 | Applicant | |
| FR2801509(A1) | 2001-06-01 | Applicant | |
| JPH08510677(A) | 1996-11-01 | Applicant | |
| JP2003503119(A) | 2003-01-01 | Applicant | |
| JP2010516353(A) | 2010-05-01 | Applicant | |
| JP2011200571(A) | 2011-10-01 | Applicant | |
| JP2012000195(A) | 2012-01-01 | Applicant | |
| WO9407564(A2) | 1994-04-01 | Applicant | |
| WO9508357(A1) | 1995-03-01 | Applicant | |
| WO9964105(A1) | 1999-12-01 | Applicant | |
| WO9965561(A1) | 1999-12-01 | Applicant | |
| WO100273(A1) | 2001-01-01 | Applicant | |
| WO2058785(A1) | 2002-08-01 | Applicant | |
| WO3094855(A1) | 2003-11-01 | Applicant | |
| WO2006110338(A1) | 2006-10-01 | Applicant | |
| WO2006115877(A1) | 2006-11-01 | Applicant | |
| WO2007053508(A1) | 2007-05-01 | Applicant | |
| WO2008092246(A1) | 2008-08-01 | Applicant | |
| WO2008094344(A1) | 2008-08-01 | Applicant | |
| WO2009006337(A1) | 2009-01-01 | Applicant | |
| WO2009134459(A2) | 2009-11-01 | Applicant | |
| WO2010029842(A1) | 2010-03-01 | Applicant | |
| WO2010148412(A1) | 2010-12-01 | Applicant | |
| WO2011158410(A1) | 2011-12-01 | Applicant | |
| WO2012106533(A2) | 2012-08-01 | Applicant | |
| WO2013131187(A1) | 2013-09-01 | Applicant | |
| WO2013188965(A1) | 2013-12-01 | Applicant | |
| WO2015075548(A1) | 2015-05-01 | Applicant | |
| WO2015109401(A1) | 2015-07-01 | Applicant |
Non-Patent Literature (58)
- Atonica A., et al., “Vagal Control of Lymphocyte Release from Rat Thymus,” Journal of the Autonomic Nervous System, Elsevier, vol. 48(3), Aug. 1994, pp. 187-197.Applicant
- Whaley K., et al., “C2 Synthesis by Human Monocytes is Modulated by a Nicotinic Cholinergic Receptor,” Nature, vol. 293, Oct. 15, 1981, pp. 580-582 (and reference page).Applicant
- Borovikovaa L.V., et al., “Role of Vagus Nerve Signaling in CNI-1493-Mediated Suppression of Acute Inflammation,” Autonomic Neuroscience: Basic and Clinical, vol. 85 (1-3), Dec. 20, 2000, pp. 141-147.Applicant
- Borovikovaa L.V., et al., “Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin,” Mature, Macmillan Magazines Ltd, vol. 405, May 25, 2000, pp. 458-462.Applicant
- Watkins L.R., et al., “Implications of Immune-to-Brain Communication for Sickness and Pain,” PNAS (Proceedings of the National Academy of Sciences of the USA), vol. 96 (14), Jul. 6, 1999, pp. 7710-7713.Applicant
- Extended European Search Report for Application No. 14864542.7, dated Jun. 2, 2017, 8 pages.Applicant
- Fleshner M., et al., “Thermogenic and Corticosterone Responses to Intravenous Cytokines (IL-1β and TNF-α) are Attenuated by Subdiaphragmatic Vagotomy,” Journal of Neuroimmunology, vol. 86, Jun. 1998, pp. 134-141.Applicant
- Gaykema R.P.A. et al., “Subdiaphragmatic Vagotomy Suppresses Endotoxin-Induced Activation of Hypothalamic Corticotropin-Releasing Hormone Neurons and ACTH Secretion,” Endocrinology, The Endocrine Society, vol. 136 (10), 1995, pp. 4717-4720.Applicant
- Gupta A.K., “Respiration Rate Measurement Based on Impedance Pneumography,” Data Acquisition Products, Texas Instruments, Application Report, SBAA181, Feb. 2011, 11 pages.Applicant
- Guslandi M., “Nicotine Treatment for Ulcerative Colitis,” The British Journal of Clinical Pharmacology, Blackwell Science Ltd, vol. 48, 1999, pp. 481-484.Applicant
- Japanese Office Action in corresponding Japanese Application No. 2014-560202, dated Dec. 6, 2016, 4 pages.Applicant
- Kawashima K., et al., “Extraneuronal Cholinergic System in Lymphocytes,” Pharmacology & Therapeutics, Elsevier, vol. 86, 2000, pp. 29-48.Applicant
- Madretsma, G.S., et al., “Nicotine Inhibits the In-vitro Production of Interleukin 2 and Tumour Necrosis Factor-α by Human Mononuclear Cells,” Immunopharmacology, Elsevier, vol. 35 (1), Oct. 1996, pp. 47-51.Applicant
- Nabutovsky, Y., et al., “Lead Design and Initial Applications of a New Lead for Long-Term Endovascular Vagal Stimulation,” PACE, Blackwell Publishing, Inc, vol. 30(1), Jan. 2007, pp. S215-S218.Applicant
- Pavlovic D., et al., “Diaphragm Pacing During Prolonged Mechanical Ventilation of the Lungs could Prevent from Respiratory Muscle Fatigue,” Medical Hypotheses, vol. 60 (3), 2003, pp. 398-403.Applicant
- Planas R.F., et al., “Diaphragmatic Pressures: Transvenous vs. Direct Phrenic Nerve Stimulation,” Journal of Applied Physiology, vol. 59(1), 1985, pp. 269-273.Applicant
- Romanovsky, A.A., et al., “The Vagus Nerve in the Thermoregulatory Response to Systemic Inflammation,” American Journal of Physiology, vol. 273 (1 Pt 2), 1997, pp. R407-R413.Applicant
- Salmela L., et al., “Verification of the Position of a Central Venous Catheter by Intra-Atrial ECG. When does this method fail?,” Acta Anasthesiol Scand, Vol. 37 (1), 1993, pp. 26-28.Applicant
- Sandborn W.J., “Transdermal Nicotine for Mildly to Moderately Active Ulcerative Colitis,” Annals of Internal Medicine, vol. 126 (5), Mar. 1, 1997, pp. 364-371.Applicant
- Sato E., et al., “Acetylcholine Stimulates Alveolar Macrophages to Release Inflammatory Cell Chemotactic Activity,” American Journal of Physiology, vol. 274 (Lung Cellular and Molecular Physiology 18), 1998, pp. L970-L979.Applicant
- Sato, K.Z., et al., “Diversity of mRNA Expression for Muscarinic Acetylcholine Receptor Subtypes and Neuronal Nicotinic Acetylcholine Receptor Subunits in Human Mononuclear Leukocytes and Leukemic Cell Lines,” Neuroscience Letters, vol. 266 (1), 1999, pp. 17-20.Applicant
- Schauerte P., et al., “Transvenous Parasympathetic Nerve Stimulation in the Inferior Vena Cava and Atrioventricular Conduction,” Journal of Cardiovascular Electrophysiology, vol. 11 (1), Jan. 2000, pp. 64-69.Applicant
- Schauerte P.N., et al., “Transvenous Parasympathetic Cardiac Nerve Stimulation: An Approach for Stable Sinus Rate Control,” Journal of Cardiovascular Electrophysiology, vol. 10 (11), Nov. 1999, pp. 1517-1524.Applicant
- Scheinman R.I., et al., “Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids,” Science, vol. 270, Oct. 13, 1995, pp. 283-286.Applicant
- Sher, M.E., et al., “The Influence of Cigarette Smoking on Cytokine Levels in Patients with Inflammatory Bowel Disease,” Inflammatory Bowel Diseases, vol. 5 (2), May 1999, pp. 73-78.Applicant
- Steinlein, O., “New Functions for Nicotinic Acetylcholine Receptors?,” Behavioural Brain Research, vol. 95, 1998, pp. 31-35.Applicant
- Sternberg E.M., (Series Editor) “Neural-Immune Interactions in Health and Disease,” The Journal of Clinical Investigation, vol. 100 (11), Dec. 1997, pp. 2641-2647.Applicant
- Sykes., A.P., et al. “An Investigation into the Effect and Mechanisms of Action of Nicotine in Inflammatory Bowel Disease,” Inflammation Research, vol. 49, 2000, pp. 311-319.Applicant
- Toyabe S., et al., “Identification of Nicotinic Acetylcholine Receptors on Lymphocytes in the Periphery as well as Thymus in Mice,” Immunology, vol. 92, 1997, pp. 201-205.Applicant
- Van Dijk A.P.M., et al., “Transdermal Nicotine Inhibits Interleukin 2 Synthesis by Mononuclear Cells Derived from Healthy Volunteers,” European Journal of Clinical Investigation, vol. 28, 1998, pp. 664-671.Applicant
- Watkins L.R., et al., “Blockade of Interleukin-1 Induced Hyperthermia by Subdiaphragmatic Vagotomy: Evidence for Vagal Mediation of Immune-Brain Communication,” Neuroscience Letters, vol. 183, 1995, pp. 27-31.Applicant
- Ayas N.T., et al., “Prevention of Human Diaphragm Atrophy with Short periods of Electrical Stimulation,” American Journal of Respiratory and Critical Care Medicine, Jun. 1999, vol. 159(6), pp. 2018-2020.Applicant
- Borovikova, et al., “Role of the Vagus Nerve in the Anti-Inflammatory Effects of CNI-1493,” Proceedings of the Annual Meeting of Professional Research Scientists: Experimental Biology 2000, Abstract 97.9, Apr. 15-18, 2000.Applicant
- Chinese Search Report for Application No. CN2013/80023357.5, dated Jul. 24, 2015.Applicant
- Co-pending U.S. Appl. No. 15/606,867, filed May 26, 2017.Applicant
- Daggeti, W.M. et al., “Intracaval Electrophrenic Stimulation. I. Experimental Application during Barbiturate Intoxication Hemorrhage and Gang,” Journal of Thoracic and Cardiovascular Surgery, 1966, vol. 51 (5), pp. 676-884.Applicant
- Daggeti, W.M. et al., “Intracaval electrophrenic stimulation. II. Studies on Pulmonary Mechanics Surface Tension Urine Flow and Bilateral Ph,” Journal of Thoracic and Cardiovascular Surgery, 1970, vol. 60(1 ), pp. 98-107.Applicant
- De Gregorio, M.A. et al., “The Gunther Tulip Retrievable Filter: Prolonged Temporary Filtration by Repositioning within the Inferior Vena Cava,” Journal of Vascular and Interventional Radiology, 2003, vol. 14, pp. 1259-1265.Applicant
- Deng Y-J et al., “The Effect of Positive Pressure Ventilation Combined with Diaphragm Pacing on Respiratory Mechanics in Patients with Respiratory Failure; Respiratory Mechanics,” Chinese critical care medicine, Apr. 2011, vol. 23(4), pp. 213-215.Applicant
- European Search Report for Application No. 13758363, dated Nov. 12, 2015.Applicant
- European Search Report for Application No. EP17169051.4, dated Sep. 8, 2017, 7 pages.Applicant
- Extended European Search Report for Application No. 15740415.3, dated Jul. 7, 2017.Applicant
- Frisch S., “A Feasibility Study of a Novel Minimally Invasive Approach for Diaphragm Pacing,” Master of Science Thesis, Simon Fraser University, 2009, p. 148.Applicant
- Furman, S., “Transvenous Stimulation of the Phrenic Nerves,” Journal of Thoracic and Cardiovascular Surgery, 1971, vol. 62 (5), pp. 743-751.Applicant
- Hoffer J.A. et al., “Diaphragm Pacing with Endovascular Electrodes”, IFESS 2010—International Functional Electrical Stimulation Society, 15th Anniversary Conference, Vienna, Austria, Sep. 2010.Applicant
- Japanese Office Action in corresponding Japanese Application No. 2014-560202, dated Oct. 17, 2017, 5 pages.Applicant
- Levine S., et al., “Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans,” New England Journal of Medicine, 2008, vol. 358, pp. 1327-1335.Applicant
- Lungpacer: Therapy, News . . . Accessed Dec. 27, 2016.Applicant
- Marcy, T.W. et al., “Diaphragm Pacing for Ventilatory Insufficiency,” Journal of Intensive Care Medicine, 1987, vol. 2 (6), pp. 345-353.Applicant
- Meyyappan R., “Diaphragm Pacing during Controlled Mechanical Ventilation: Pre-Clinical Observations Reveal a Substantial Improvement in Respiratory Mechanics”, 17th Biennial Canadian Biomechanics Society Meeting, Burnaby, BC, Jun. 6-9, 2012.Applicant
- Notification of Reasons for Rejection and English language translation issued in corresponding Japanese Patent Application No. 2015-517565, dated Mar. 28, 2017, 6 pages.Applicant
- Onders R.,, “A Diaphragm Pacing as a Short-Term Assist to Positive Pressure Mechanical Ventilation in Critical Care Patients,” Chest, Oct. 24, 2007, vol. 132(4), pp. 5715-5728.Applicant
- Onders R.,, “Diaphragm Pacing for Acute Respiratory Failure,” Difficult Decisions in Thoracic Surgery, Chapter 37, Springer-Verlag, 2011, M.K. Ferguson (ed.), pp. 329-335.Applicant
- Onders R, et al., “Diaphragm Pacing with Natural Orifice Transluminal Endoscopic Surgery: Potential for Difficult-to-Wean Intensive Care Unit Patients,” Surgical Endoscopy, 2007, vol. 21, pp. 475-479.Applicant
- Sandoval R., “A Catch/Ike Property-Based Stimulation Protocol for Diaphragm Pacing”, Master of Science Coursework project, Simon Fraser University, Mar. 2013.Applicant
- Sarnoff, S.J. et al., “Electrophrenic Respiration,” Science, 1948, vol. 108, p. 482.Applicant
- Wanner, A. et al., “Trasvenous Phrenic Nerve Stimulation in Anesthetized Dogs,” Journal of Applied Physiology, 1973, vol. 34 (4), pp. 489-494.Applicant
- PCT Search Report dated Oct. 26, 2018 for PCT Application No. PCT/IB2018/000603, 7 pages.Applicant