ANEURYSM OCCLUSION DEVICE

Abstract

An occlusion device suitable for endovasculature treatment of an aneurysm in a blood vessel in a patient, including a substantially tubular structure having a proximal end region and a distal end region, having a first, expanded condition and a second, collapsed condition. The device has dimensions in the second, collapsed condition suitable for insertion through vasculature of the patient and through a neck of the aneurysm. The device further includes a control ring having a substantially annular body disposed on the proximal end region of the structure and at least substantially circumscribing the proximal end region to prevent radial expansion of the proximal end region and to provide an engagement feature during manipulation of the occlusion device.

Claims

1. A system suitable for endovascular treatment of an aneurysm in a blood vessel in a patient, comprising: an occlusion device having a substantially tubular braided mesh structure having a proximal end region and a distal end region and a control ring having a substantially annular body disposed on the proximal end region of the tubular structure, the control ring at least partially circumscribing the proximal end region to prevent radial expansion of the proximal end region and to provide an engagement feature during manipulation of the occlusion device; a delivery member having a distal end region carrying a grabber having at least two finger elements, each finger element including a notch configured to engage the control ring such that the occlusion device and delivery member are in mechanical communication, the notch having an inner top surface and an inner bottom surface defining an inner cavity having a height approximately equal to a thickness of the control ring; and an embolic implant delivery catheter capable of delivering an embolic implant to the aneurysm, wherein the tubular structure is expandable from a collapsed condition to an expanded condition, wherein in the collapsed condition, the tubular structure is suitable for insertion through vasculature of a patent and through a neck of the aneurysm, and wherein in the expanded condition, the tubular structure has a substantially hemispherical shape and has an exterior surface capable of contacting the aneurysm and capable of providing a force to appose the embolic implant delivery catheter to the aneurysm.

2. The system of claim 1 wherein the tubular structure of the occlusion device in the expanded condition is capable of supporting the embolic implant in the aneurysm.

3. The system of claim 1 wherein the control ring is crimped onto the proximal end region of the tubular structure.

4. The system of claim 1 wherein the control ring includes radiopaque material.

5. The system of claim 1 wherein the tubular structure includes a plurality of filaments.

6. The system of claim 1 wherein the tubular structure defines a substantially enclosed volume.

7. The system of claim 1 wherein at least a portion of the proximal end region of the tubular structure defines a plurality of openings having a sufficiently small size to enhance occlusion of the aneurysm.

8. The system of claim 1 wherein the delivery member is a tube formed of at least one metallic material.

9. The system of claim 1 wherein the grabber is formed of a metallic material.

10. The system of claim 1 further including an occlusion device delivery catheter having an inner lumen through which the delivery member is insertable and translatable relative to the occlusion device delivery catheter.

11. A system suitable for endovascular treatment of an aneurysm in a blood vessel in a patient, comprising: an occlusion device having a substantially tubular structure having a proximal end region and a distal end region and a control ring having a substantially annular body disposed on the proximal end region of the tubular structure, the control ring at least partially circumscribing the proximal end region to prevent radial expansion of the proximal end region and to provide an engagement feature during manipulation of the occlusion device; and a delivery member having a distal end region carrying a grabber having at least two finger elements, each finger element including a notch configured to engage the control ring such that the occlusion device and delivery member are in mechanical communication, the notch having an inner top surface and an inner bottom surface defining an inner cavity having a height approximately equal to a thickness of the control ring; and an embolic implant delivery catheter capable of delivering an embolic implant to the aneurysm, wherein the tubular structure is expandable from a collapsed condition to an expanded condition.

12. The system of claim 11 wherein in the collapsed condition, the tubular structure is suitable for insertion through vasculature of a patent and through a neck of the aneurysm.

13. The system of claim 11 wherein the expanded condition, the tubular structure has a substantially hemispherical shape and has an exterior surface capable of contacting the aneurysm and capable of providing a force to appose the embolic implant delivery catheter to the aneurysm.

14. The system of claim 11 wherein the tubular structure of the occlusion device in the expanded condition is capable of supporting the embolic implant in the aneurysm.

15. The system of claim 11 wherein the control ring is crimped onto the proximal end region of the tubular structure.

16. The system of claim 11 wherein the control ring includes radiopaque material.

17. The system of claim 11 wherein at least a portion of the proximal end region of the tubular structure defines a plurality of openings having a sufficiently small size to enhance occlusion of the aneurysm.

18. The system of claim 11 wherein the delivery member is a tube formed of at least one metallic material.

19. The system of claim 11 wherein the tubular structure is a braided mesh structure including a plurality of filaments.

20. The system of claim 11 further including an occlusion device delivery catheter having an inner lumen through which the delivery member is insertable and translatable relative to the occlusion device delivery catheter.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In what follows, preferred embodiments of the invention are explained in more detail with reference to the drawings and photographs, in which:

[0018] FIG. 1 is a schematic side cross-sectional view of an inventive occlusion device within a novel catheter delivery system positioned at the neck of an aneurysm of a blood vessel;

[0019] FIG. 2 is an enlarged schematic side view of the delivery system of FIG. 1 showing the occlusion device held in a collapsed condition;

[0020] FIG. 3 is a schematic side view similar to FIG. 1 showing the occlusion device according to the present invention expanding within the sac of the aneurysm while still being securely held by the delivery system;

[0021] FIG. 4 is a schematic side view similar to FIG. 3 showing an embolic coil being advanced through the delivery system and the occlusion device into the aneurysm;

[0022] FIG. 5 is a schematic side view similar to FIG. 2 with the microcatheter withdrawn proximally to allow grasper fingers to release the control ring of the occlusion device;

[0023] FIG. 6 is a schematic side cross-sectional view similar to FIG. 4 after the delivery system has been withdrawn and with embolic coils securing the occlusion device within the sac of the aneurysm;

[0024] FIG. 7 is a schematic cross-sectional view of a spherical mandrel establishing the first, expanded condition for at least one an occlusion device according to the present invention;

[0025] FIGS. 8A and 8B are schematic side views of two hemi-spherical occlusion devices according to the present invention derived from the occlusion device of FIG. 7;

[0026] FIG. 9 is a schematic side view of a single occlusion device after the mandrel of FIG. 7 has been removed;

[0027] FIG. 10 is a schematic side view similar to FIG. 9 after a distal portion of the occlusion device has been removed to generate an alternative open configuration;

[0028] FIG. 11 is a side view similar to FIG. 10 of an alternative occlusion device formed utilizing an elliptical, lozenge-shaped mandrel;

[0029] FIG. 12 is a view similar to FIG. 3 showing the occlusion device cooperating with a cage-like vaso-occlusive structure within an aneurysm;

[0030] FIG. 13 is an enlarged schematic side view of an alternative delivery system for devices similar to those shown in FIG. 12 with an occlusion device and a vaso-occlusive structure held in a collapsed condition being advanced into an aneurysm;

[0031] FIG. 14 is a schematic side cross-sectional view similar to FIG. 13 after the delivery system has been withdrawn, and with the vaso-occlusive structure securing the occlusion device within the sac of the aneurysm;

[0032] FIG. 15 is a schematic side cross-sectional view of an inventive occlusion device within a novel catheter delivery system positioned at the neck of an aneurysm of a blood vessel and a catheter for delivering an embolic device inserted into the aneurysm sac;

[0033] FIG. 16 is a schematic side cross-sectional view showing the occlusion device of FIG. 15 positioned at the neck of an aneurysm of a blood vessel in a partially implanted condition and a catheter for delivering an embolic device inserted into the aneurysm sac;

[0034] FIG. 17A is a schematic side view showing the occlusion device of FIG. 16 expanded within the sac of the aneurysm while still being securely held by the delivery system and the catheter for delivering the embolic device jailed between the expanded occlusion device and a wall of the aneurysm;

[0035] FIG. 17B is a cross-sectional view of the expanded occlusion device and jailed catheter of FIG. 17A;

[0036] FIG. 18 is a schematic side view showing the expanded occlusion device of FIG. 17A and an embolic coil being advanced through the embolic delivery catheter and the occlusion device into the aneurysm;

[0037] FIG. 19 is a schematic side view showing the expanded occlusion device of FIG. 18 after completion of implantation and removal of catheters; and

[0038] FIG. 20 is a schematic side view showing the release of an expanded occlusion device such as the occlusion device illustrated in FIGS. 15-19.

DETAILED DESCRIPTION

[0039] This invention may be accomplished by an occlusion device suitable for endovascular treatment of an aneurysm in a blood vessel in a patient, with a substantially tubular structure having a proximal end region and a distal end region, having a first, expanded condition and a second, collapsed condition. The device has dimensions in the second, collapsed condition suitable for insertion through vasculature of the patient, utilizing a catheter such as a microcatheter, and through a neck of the aneurysm. The device further includes a control ring having a substantially annular body disposed on the proximal end region of the structure and at least substantially circumscribing the proximal end region to prevent radial expansion of the proximal end region and to provide an engagement feature during manipulation of the occlusion device.

[0040] The control ring is releasably engageable by a releasable feature such as a grabber or at least one frangible member on a delivery member in some mechanical constructions or, in other constructions, by at least one electrolytically severable element. Preferably, the control ring defines an inner passage through which at least one embolic coil is insertable into the aneurysm. In another construction, the occlusion device is held in place within the aneurysm by at least one vaso-occlusive structure such as a cage-like device.

[0041] FIG. 1 schematically illustrates the distal portion of a novel delivery system 10 including a microcatheter 12 and a delivery tube 14 holding a tubular occlusion device 20 according to the present invention to be implanted within sac S of aneurysm A emerging from blood vessel BV. In one construction, the microcatheter 12 has a distal radiopaque marker band 13 and is advanced to the vicinity of neck N of aneurysm A such that marker band 13 is at the level of the neck N as seen under fluoroscopy.

[0042] Enlarged views of the distal portion of delivery system 10 and of occlusion device 20 are provided in FIGS. 2 and 5. Occlusion device 20 is shown in a second, collapsed condition in FIG. 2 within catheter lumen 11, with a control ring 22 held by grabber 30 of delivery tube 14. Control ring 22 is disposed about a proximal region 23 of device structure 25 and defines an inner passage 26 through which one or more embolic coils are inserted, as described in more detail below. Structure 25 of occlusion device 20 further includes a mesh body 24 and a distal region 28.

[0043] After the delivery system 10 is positioned as shown in FIG. 1, the delivery tube 14 is advanced within lumen 11 of catheter 12 to enable occlusion device 20 to expand into an approximately hemi-spherical shape within sac S as shown in FIG. 3. The shape of occlusion device 20 will conform to the shape of the sac S where device 20 touches the inner wall of the sac S. Grabber 30 continues to be constrained radially by lumen 11 of catheter 12 and maintains its grip on control ring 22 with a plurality of gripping regions such as notches 36 and 38, FIG. 5. In one construction, control ring 22 is radiopaque and is aligned under fluoroscopy relative to marker 13 on catheter 12 as shown in FIGS. 3 and 4.

[0044] Once occlusion device 20 is positioned within sac S, at least one embolic coil 40, FIG. 4, is advanced through lumen 15 of delivery tube 14 as indicated by arrow 42, through passage 26 of control ring 22 as indicated by arrow 44, and is advanced, arrow 46, within aneurysm A to substantially fill sac S and to anchor body 24 of occlusion device 20 against the interior wall of aneurysm A to block neck N as shown in FIG. 6.

[0045] After a sufficient amount of embolic coil 40 has been fully deployed within sac S to anchor occlusion device 20 within aneurysm A, the catheter 12 is withdrawn proximally, as indicated by arrow 51 in FIG. 5, while maintaining delivery tube 14 in place, to remove radial constraint on fingers 32 and 34 of grabber 30. Fingers 32 and 34 preferably are biased radially outwardly and move in the direction of arrows 50 and 52, respectively, to disengage control ring 22 from notches 36 and 38 in fingers 32 and 34, respectively.

[0046] In one construction, the catheter 12 is a polymeric microcatheter defining an inner lumen 11 having an inner diameter of between 0.020 inch and 0.027 inch, the delivery tube 14 has outer diameter that is slightly less than the inner diameter of the catheter lumen 11, and the grabber 30 with occlusion device 20 in the collapsed condition shown in FIGS. 1 and 2 also have outer diameters that are substantially the same as the inner diameter of the catheter lumen 11, which radially constrains fingers 32 and 34 to engage control ring 22. The lumen 15 of delivery tube 14 has a diameter capable of allowing passage of a conventional embolic coil delivery system having a nominal outer diameter of between 0.010 inch and 0.015 inch.

[0047] In some constructions, the delivery tube has at least one region of increased flexibility, especially near the distal end of the delivery tube, to minimize unintended microcatheter movement during translation of the delivery tube relative to the microcatheter. The at least one flexible region is made in one construction by laser-cutting a pattern of interrupted cuts into a medical-grade nitinol (NiTi) tube. In other constructions, a coiled metallic or polymeric cylindrical component and/or a cylindrical section of flexible polymeric material is added to the distal region of the delivery tube. The grabber is created in some constructions by laser-cutting material forming the grabber to create at least two finger elements, each preferably having a notch to enhance gripping of a control ring according to the present invention. In certain constructions, the grabber is integral, that is, is monolithically formed with the same material as the remainder of the delivery tube and, in other constructions, is fixedly attached to the distal end of the delivery tube.

[0048] In one construction, the structure 25 of occlusion device 20 is formed of metallic filaments that establish an expandable braided mesh tube. Suitable materials for the filaments include nitinol wires and other biocompatible metals, such as platinum, that will not remain in a collapsed condition after being ejected from a delivery tube. Preferably, at least one platinum wire is included for radiopacity. In other constructions, the structure 25 is formed of at least one polymeric material that does not become “set” in the collapsed condition.

[0049] Suitable materials for control ring 22 discussed above, and for control ring 22a and band 22b discussed below in relation to FIGS. 7-8B, include biocompatible radiopaque materials such as platinum, tantalum and gold. Other suitable metallic materials include cobalt chromium, stainless steel, and combinations of two or more of biocompatible metals. Suitable polymeric materials include biocompatible biodegradable and non-biodegradable materials, as described in more detail below.

[0050] One technique for manufacturing an occlusion device according to the present invention is illustrated in FIG. 7. After structure 25a is formed as a braided mesh tube, a control ring 22a is disposed by crimping and/or welding ring material about proximal region 23a to limit radial expansion at that site while defining an inner passage 26a through which one or more embolic coils can be inserted, as described above. Optionally, an inner sleeve such as a grommet (not shown) is inserted within structure 25a and positioned under the control ring 23a to maintain an inner diameter opening of desired dimension for inner passage 26a.

[0051] In this technique, a spherical mandrel 60 such as a steel ball bearing is inserted through distal region 28a to enlarge and expand the structure 25a in body region 24a. A clamp-like element such as a band 22b is then crimped over distal region 62 to further shape the body 24a. In some techniques, the assembly is heated to set mesh body 24a in the expanded condition.

[0052] When two hemispherical occlusion devices are desired, a cut is made along the circumference of mandrel 60, typically equidistant between control ring 22a and band 22b as indicated by dashed line 63, as well as on the opposite sides of control ring 22a and band 22b as shown by arrows 64 and 66, respectively. This technique creates two separate devices 20a and 20b, as depicted in FIGS. 8A and 8B, respectively. Distal end regions 28a and 28b are both open, such as illustrated for device 20 in FIGS. 1-6. Device 20b also has body 24b, proximal region 23b, and a passage 26b formed by band 22b which serves as a control ring according to the present invention. In other words, band 22b is incorporated into an implantable device 20b in one construction, instead of being a temporary clamp.

[0053] In alternative techniques, band 22b is removed and mandrel 60, FIG. 7, is extracted to form the occlusion device 20c, FIG. 9, with a constricted yet un-constrained distal region 28c, having a single control ring 22a. In yet another technique, a cut is made non-equatorially about structure 25a, such as along line 70, to generate device 20d, FIG. 10. In yet other constructions, a non-spherical mandrel such as a lozenge-shaped mandrel, is utilized to form an elongated device 20e, FIG. 11. In other words, the occlusion device according to the present invention can have many shapes such as round, elliptic, oblong, or otherwise asymmetric, and can have an open or a closed distal end. It is expected that an open distal end will typically allow better conformance to the neck and sac of the aneurysm to be treated.

[0054] An alternative occlusion device 20f according the present invention is illustrated in FIG. 12 cooperating with a cage-like vaso-occlusive structure 80 formed of strands 82, 84, 86, 88, 90, 92 and 94 in this construction. In some constructions, vaso-occlusive structure 80 is similar to one of the embodiments disclosed in U.S. Pat. No. 5,645,558 by Horton and, in certain other constructions, is similar to one of the embodiments disclosed in U.S. Pat. No. 5,916,235 by Guglielmi and in U.S. Patent Publication No. 2010/0069948 by Veznedaroglu et al.

[0055] After a delivery system 10f is positioned as desired relative to aneurysm A, an elongated delivery member 14f is advanced within lumen 11f of catheter 12f to enable occlusion device 20f and vaso-occlusive structure 80 to expand within sac S as shown in FIG. 12. In this construction, a grabber 30f continues to be constrained radially by lumen 11f of catheter 12f and maintains its grip on control ring 22f with a plurality of gripping regions. In one construction, control ring 22f is radiopaque and is aligned under fluoroscopy in a similar manner as described above relative to FIGS. 3 and 4.

[0056] Once vaso-occlusive structure 80 is fully deployed in an expanded condition within sac S, structure 80 presses occlusion device 20f against the interior wall and across the neck N of aneurysm A to secure it in place. In other words, vaso-occlusive structure 80 serves in an expanded condition as a frame or lattice to anchor occlusion device 20f against neck N, and occlusion device 20f, held in place by structure 80, serves as a cover extending at least across neck N, the cover preferably being porous or otherwise defining sufficiently small openings, to enhance occlusion of aneurysm A. Preferably, occlusion device 20f is secured to vaso-occlusive structure 80 by at least one attachment point, being attached to at least one of a portion of the interior surface of device 20f and a portion of the control ring 22f, to maintain an aligned relationship between the device 20f and the structure 80, especially during loading and delivery of structure 80 and device 20f utilizing a delivery cannula.

[0057] In certain techniques, if a surgeon or other user desires to substantially fill the interior of sac S, at least one embolic coil is advanced through lumen 15f of delivery tube 14f, through a passage in control ring 22f, and then is advanced into aneurysm A. In other constructions, for use where insertion of one or more embolic coils is not desired, control ring 22f may lack a passage.

[0058] In yet other constructions, such as illustrated in FIGS. 13-14, an occlusion device 20g has a detachment feature 98, representing a conventional detachment joint, instead of a control ring. Examples of electrolytically severable joints and mechanical joints are described in U.S. Pat. No. 6,454,780 by Wallace and in U.S. Pat. No. 7,410,482 by Murphy et al., for example. Similar detachable joints are described in U.S. Pat. No. 5,916,235 by Guglielmi for cage-like vaso-occlusive structures.

[0059] After the delivery system 10g is positioned within blood vessel BV as shown in FIG. 13, a delivery member 14g, also referred to as a pusher 14g, is advanced within lumen 11g of catheter 12g to enable occlusion device 20g and vaso-occlusive structure 80g to expand within aneurysm A as shown in FIG. 14. The connection between severable element 96 and detachment feature 98 is then severed, mechanically and/or electrolytically.

[0060] Body 24g is formed of a wire mesh or braid in some constructions. In yet other constructions, the body of the occlusive device is a biocompatible film made from one or more polymeric substances. Suitable biocompatible compositions for film material include films or matrices of cellulose, alginate, cross-linked gels, and very thin polymer films of materials such as urethane, polycaprolactone (PCL), poly-lactic acid (PLA) and/or poly-glycolic acid (PGA). The film need not be erodible or bioabsorbable. In some constructions, microscopic pores or other openings are formed in the film having average diameters which are uniform in some constructions and non-uniform in other constructions. The geometric size of the pores is substantially constant along the length of the structure in some embodiments and, in other embodiments, varies along the length. The number of pores is substantially uniform along the length of the structure in some embodiments and, in other embodiments, varies along the length. Other potential materials include polysaccharides, colloidal compounds, and some lipid products. In an alternate configuration, at least the body of the occlusive device is made of a durable, non-erodible, non-bioabsorbable material, such as a solidified urethane foam or expanded polytetrafluoroethylene (PTFE). In some embodiments, the material defines openings at least 10 microns in diameter prior to implantation in the patient and has a thickness ranging between 10 microns to 500 microns.

[0061] FIG. 15 schematically illustrates the distal portion of a novel delivery system 10h including an occlusion device delivery catheter 12h, a delivery tube 14h positioned within a lumen 11h of the occlusion device delivery catheter 12h holding a tubular occlusion device 20h, and an embolic implant delivery catheter 41h according to the present invention. As illustrated, the embolic implant delivery catheter 41h can be delivered to the aneurysm A separately from the occlusion device 20h. A distal end of the embolic implant delivery catheter 41h can be inserted into the sac S of the aneurysm A, and the occlusion device delivery catheter 12h can be positioned to implant the occlusion device 20h within sac S of aneurysm A. In one construction, the microcatheter 12h has a distal radiopaque marker band 13h and is advanced to the vicinity of neck N of aneurysm A such that marker band 13h is at the level of the neck N as seen under fluoroscopy.

[0062] After the delivery system 10h is positioned as shown in FIG. 15, the delivery member 14h is advanced within lumen 11h of catheter 12h to enable occlusion device 20h to expand into an approximately hemi-spherical shape within sac S. FIG. 16 illustrates the expansion of a distal end region 28h of the occlusion device 20h as it exits the occlusion device delivery catheter 12h. FIG. 17A illustrates the tubular body region 24h of the occlusion device 20h expanded to such that an exterior surface of the occlusion device 20h contacts the aneurysm A and the embolic implant delivery catheter 41h. The shape of occlusion device 20h will conform to the shape of the sac S where device 20h touches the inner wall of the sac S and will conform to the embolic implant delivery catheter 41h where device 20h touches the embolic catheter 41h. FIG. 17B is a cross-sectional view of FIG. 17A illustrating the conformity of the device 20h to the inner wall of the sac S and the embolic implant delivery catheter 41h. The body region 24h of the occlusion device 20h is in the expanded condition provides a force to appose the embolic catheter 41h to the aneurysm wall.

[0063] Once occlusion device 20h is positioned within sac S, at least one embolic coil 40h, FIG. 18, is advanced through a lumen of the embolic implant delivery catheter 41h to substantially fill sac S and to anchor body 24h of occlusion device 20h against the interior wall of aneurysm A to block neck N as shown in FIG. 19. As is apparent, once the embolic coil 40h is delivered, the embolic implant delivery catheter 41h can be removed. Once removed from the sac S, the occlusion device 20h can conform to the remaining section of the inner wall.

[0064] Referring collectively to FIGS. 15-18, during implantation of the occlusion device 20h and the embolic coil 40h a control ring 22h near a proximal end region 23h of the occlusion device 20h can be held by a grabber 30h on the delivery member 14h. After a sufficient amount of embolic coil 40h has been fully deployed within sac S to anchor occlusion device 20h within aneurysm A, the occlusion device 14h can be released from the delivery member 14h. The grabber 30h can be constrained by the occlusion device delivery catheter 12h, and fingers 32h and 34h of the grabber 30h can expand when exiting the occlusion device delivery catheter 12h to release the control ring 22h as shown in FIG. 20. The grabber 30h can have a plurality of gripping regions such as notches 36h and 38h. In one construction, control ring 22h is radiopaque and is aligned under fluoroscopy relative to marker 13h on catheter 12h as shown in FIGS. 15-18 and 20. Fingers 32h and 34 preferably are biased radially outwardly to disengage control ring 22h from notches 36h and 38h in fingers 32h and 34h, respectively.

[0065] An advantage of the system 10h illustrated in FIGS. 15-20 is that the occlusion device delivery catheter 12h, the control ring 22h, and the delivery member 14h need not be sized to deliver an embolic implant. Because the delivery member 14h need not be sized to delivery an embolic implant, numerous alternative delivery or pusher apparatus can be used in place of or in addition to the delivery members and delivery tubes described herein.

[0066] In one construction, the tubular structure, mesh body region 24h of occlusion device 20h is formed of metallic filaments that establish an expandable braided mesh tube. Suitable materials for the filaments include nitinol wires and other biocompatible metals, such as platinum, that will not remain in a collapsed condition after being ejected from a delivery tube. Preferably, at least one platinum wire is included for radiopacity. In other constructions, the tubular structure 24h is formed of at least one polymeric material that does not become “set” in the collapsed condition.

[0067] Thus, while there have been shown, described, and pointed out fundamental novel features of the invention as applied to a preferred embodiment thereof, it will be understood that various omissions, substitutions, and changes in the form and details of the devices illustrated, and in their operation, may be made by those skilled in the art without departing from the spirit and scope of the invention. For example, it is expressly intended that all combinations of those elements and/or steps that perform substantially the same function, in substantially the same way, to achieve the same results be within the scope of the invention. Substitutions of elements from one described embodiment to another are also fully intended and contemplated. It is also to be understood that the drawings are not necessarily drawn to scale, but that they are merely conceptual in nature. It is the intention, therefore, to be limited only as indicated by the scope of the claims appended hereto.

[0068] Every issued patent, pending patent application, publication, journal article, book or any other reference cited herein is each incorporated by reference in their entirety.