SYSTEM

PRIORITY

[0001] The present application claims priority under 35 U.S.C. § 119(e) to U.S.

Provisional Patent Application No. 62/859,968, filed on June 11, 2019, titled“SYSTEMS AND METHODS FOR DELIVERY OF CHORDEA REPLACEMENT SYSTEM,” which is hereby incorporated by reference herein in its entirety.

BACKGROUND

[0002] The present invention relates to implantable devices. The invention is particularly useful in devices implantable by catheter for the treatment of mitral or tricuspid regurgitation. The cause of the regurgitation can be functional, degenerative, or any other reason. The invention could be used for valvular lesions as well.

[0003] Mitral regurgitation is a valvular dysfunction that causes blood volume to flow during systole (i.e., left ventricular contraction) from the left ventricle to the left atrium, in contrast to a healthy heart where this direction of flow is blocked by the mitral valve. The reversed flow during systole causes a rise in pressure in the left atrium. Maintaining a normal cardiac output results in increased left ventricle pressure.

[0004] Treating patients with mitral or tricuspid regurgitation could require valve repair or replacement in order to reduce or eliminate the regurgitation. For many years, the commonly accepted treatment was surgical repair or replacement of the native valve during open heart surgery. Valve repair is a procedure that may require complementary treatments such as utilizing annuloplasty rings with or without leaflet or chordae repair. In recent years, a trans vascular technique has been developed for introducing these devices in general and implanting an artificial chorda through a catheter in a manner that is less invasive than open heart surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0005] Aspects, features, benefits and advantages of the embodiments described herein will be apparent with regard to the following description, appended claims, and accompanying drawings where:

[0006] FIG. 1 depicts a short axis view of the heart in accordance with an

embodiment.

[0007] FIG. 2 depicts mitral valve leaflets of the heart in accordance with an embodiment.

[0008] FIG. 3 depicts a long axis anterior to posterior view of the heart in accordance with an embodiment.

[0009] FIG. 4 depicts a long axis commissure to commissure view of the heart in accordance with an embodiment.

[0010] FIG. 5 depicts an illustrative transatrial approach in a commissure to commissure view of the heart in accordance with an embodiment.

[0011] FIG. 6 depicts an illustrative transatrial approach in an anterior to posterior view of the heart in accordance with an embodiment.

[0012] FIG. 7 depicts an illustrative transapical approach in a commissure to commissure view of the heart in accordance with an embodiment.

[0013] FIG. 8 depicts an illustrative transfemoral approach in an anterior to posterior view of the heart in accordance with an embodiment.

[0014] FIG. 9 depicts an illustrative posterior leaflet with a plurality of artificial chordae being implanted in accordance with an embodiment. [0015] FIG. 10 depicts a side view of a posterior leaflet with an artificial chordae being implanted in accordance with an embodiment.

[0016] FIG. 11 depicts an illustrative artificial chordae with a leaflet capture mechanism in accordance with an embodiment.

[0017] FIG. 12 depicts an illustrative open leaflet capture configuration on an artificial chordae in accordance with an embodiment.

[0018] FIG. 13 depicts an illustrative closed leaflet capture configuration on an artificial chordae in accordance with an embodiment.

[0019] FIG. 14 depicts an illustrative pulley-based attachment and tuning mechanism in accordance with an embodiment.

[0020] FIG. 15 depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment.

[0021] FIG. 16 depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment.

[0022] FIG. 17 depicts another illustrative anchor-based attachment and tuning mechanism in accordance with an embodiment.

[0023] FIG. 18 depicts an illustrative anchor subassembly for an artificial chordae in accordance with an embodiment.

[0024] FIG. 19 depicts an illustrative inner member of an anchor subassembly in a deployed configuration in accordance with an embodiment.

[0025] FIG. 20 depicts an illustrative inner member of an anchor subassembly in a non-deployed configuration in accordance with an embodiment. [0026] FIG. 21 depicts an illustrative outer member of an anchor subassembly in accordance with an embodiment.

[0027] FIG. 22 depicts an illustrative anchor subassembly in a non-deployed configuration in accordance with an embodiment.

[0028] FIG. 23 depicts an illustrative anchor subassembly in a deployed

configuration in accordance with an embodiment.

DETAILED DESCRIPTION

[0029] This disclosure is not limited to the particular systems, devices, and methods described, as these may vary. The terminology used in the description is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope.

[0030] As used in this document, the singular forms“a,”“an,” and“the” include plural references unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Nothing in this disclosure is to be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention. As used in this document, the term“comprising” means“including, but not limited to.”

[0031] When the term“valvular apparatus” is used in different variations, it may refer to the mitral valve apparatus and/or to the tricuspid valve apparatus and include the leaflets, the chordae, and/or the papillary muscles.

[0032] In an embodiment, an artificial chordae device is delivered to the target site, the mitral or tricuspid valve apparatus, through a catheter while the artificial chordae and their anchoring accessories are housed within a low diameter shaft which is correctly positioned and anchored to the functional configuration geometry and location. The catheter may be advanced to the target site through the vascular system. In an embodiment, the catheter may be advanced from the femoral vein or artery. In alternate embodiments, the catheter may be advanced from any blood vessel that allows access to the target site. In some embodiments the catheter may be advanced transapically, where a catheter is advanced through a small incision made in the chest wall and then through the apex. In some embodiments, the catheter may be advanced transatrially, where a catheter is advanced through a small incision made in the chest wall and then through the left or right atrium.

[0033] The artificial chordae device may include one or more of a variety of attachment methods for attachment to the native leaflet and myocardium. The artificial chordae device may include one or more of a variety of locking mechanisms between the leaflet capture subassembly and the native leaflet. In some embodiments, the artificial chordae device may include barbs to prevent rocking and device movement in relation to the leaflet upon insertion. The artificial chordae device may include one or more of a variety of tuning mechanisms. In addition, the artificial chordae device may include one or more of a variety of features that lock the tuning mechanism. Examples of the above-identified variations will be described further herein, although the described variations are illustrative only and are not meant to be limiting.

[0034] The illustrated example embodiments will be best understood by reference to the figures. The following description is intended only by way of example and illustrates certain example embodiments.

[0035] FIG. 1 depicts a short axis view of the heart displaying the four valves: the mitral valve 121, the tricuspid valve 109, the pulmonary valve 110, and the aortic valve 107. As shown, the mitral valve 121 includes the posterior leaflet 104 and the anterior leaflet 105, which will be discussed further herein in relation to various embodiments.

[0036] FIG. 2 depicts a perspective of the mitral valve commonly known as the “surgical view” which identifies individual segments of the native leaflets of the mitral valve 221. As depicted in FIG. 2, individual segments (Al, A2, A3) of the anterior leaflet 205 and individual segments (PI, P2 and P3) of the posterior leaflet 204 are identified. The lateral commissure 219 and medial commissure 220 are also noted for reference.

[0037] FIG. 3 depicts a left ventricular outflow tract view, anterior to posterior, of the heart which shows how the anterior 305 and posterior 304 leaflets are attached to the papillary muscles 303 by the chordae 306. FIG. 3 further depicts the left ventricle 302 and the right ventricle 301 separated by the intraventricular septum 312, the apex 316, the left atrium 308, and the aortic valve 307. Within the left ventricle 302, the posterior wall 311, mitral groove 314, and aortic-mitral continuity 315 are specifically identified.

[0038] FIG. 4 depicts a perspective of the left side of the heart in commissure to commissure view showing the left atrium 408. Similar to FIG. 3, FIG. 4 depicts the attachment of the posterior leaflet 404 to the myocardium 403 via the chordae 406 near the apex of the heart 416.

[0039] FIG. 5 depicts an illustrative transatrial approach of a chordae repair device to the mitral valve apparatus in a commissure to commissure view of the heart in accordance with an embodiment. When using the transatrial approach, a catheter 545 is introduced into the left atrium 508 directly. In addition, the transatrial approach may pass by or cross-over the mitral valve and allow implantation of a chordae repair device between the posterior leaflet 504 and/or the papillary muscles 503 to repair the chordae 506. [0040] FIG. 6 depicts an illustrative transatrial approach of a chordae repair device to the mitral valve apparatus in an anterior to posterior view of the heart in accordance with an embodiment. The catheter 645 is introduced into the left atrium 608 directly at the native valve comprising the anterior 605 and posterior 604 leaflets. Using this approach, implantation of aa chordae repair device may be made to the leaflets 604, 605 and the papillary muscles 603 in repair of the chordae 606 within the left ventricle 602. FIG. 6 further depicts the right ventricle 601 and aortic valve 607 for reference.

[0041] FIG. 7 depicts an illustrative transapical approach of a chordae repair device to the mitral valve apparatus in an anterior to posterior view of the heart in accordance with an embodiment. Using the transapical approach, the catheter 745 is introduced between the left atrium 708 and the ventricle 702. The transapical approach is a direct approach where the catheter 745 is introduced into the left ventricle across the apex 716 to allow implantation of the chordae repair device to the valvular apparatus to anchor between the leaflet 704 (e.g., posterior leaflet, interior leaflet, etc.) and the papillary muscles 703 to repair the chordae 706.

[0042] FIG. 8 depicts an illustrative transfemoral approach of the chordae repair device to the mitral valve apparatus in an anterior to posterior view of the heart in accordance with an embodiment. The transfemoral approach is a percutaneous approach where the catheter 845 is introduced into the femoral vein and advanced along the inferior vena cava to the right atrium, across the septum 812, to allow implantation of a chordae repair device to the valvular apparatus including the anterior 805 and posterior 804 leaflets, papillary muscles 803, and chordae 806. The aortic valve 807 is also shown for reference.

[0043] FIG. 9 depicts an illustrative posterior leaflet with a plurality of artificial chordae being implanted in accordance with an embodiment. As shown in FIG. 9, an artificial chordae device 922 is implanted at a plurality of locations on the posterior leaflet 904 of the left ventricle 902. The artificial chordae device 922 may be used to repair chordae 906 that failed due to, for example and without limitation, leaflet prolapse, flail, or other pathology. In some embodiments, the artificial chordae device 922 comprises a plurality of artificial chordae 944, an anchor subassembly 923 configured to attach to the myocardium, and a leaflet capture subassembly 935, with a tuning mechanism 942 and stress relief pad 938, configured to attach to the native leaflet. The implantation of one or more artificial chordae devices 922 may be performed serially or in parallel. Each artificial chordae device 922 may be tuned separately using the corresponding tuning mechanism 942. The one or more artificial chordae devices 922 may be visualized using, for example and without limitation, endoscopy, fluoroscopy, a CT scan, an MRI scan, and/or vital signals to assist in optimizing the result.

[0044] FIG. 10 depicts a side view of a posterior leaflet with an artificial chordae device being implanted in accordance with an embodiment. As shown in FIG. 10, one or more leaflet capture assemblies 1035 may be attached to the posterior leaflet 1004 in the left ventricle 1002 from a side view. The one or more leaflet capture assemblies 1035 may include a mechanism to ensure connectivity and proper tension. In some embodiments, the connectivity and tension may be tunable (e.g., separately or in combination) during and/or after deployment and attachment. An anchor assembly 1023 may be used to attach the artificial chordae 1044 to the myocardium. The anterior leaflet 1005 and aortic valve 1007 are shown for reference.

[0045] FIG. 11 depicts an illustrative artificial chordae with a leaflet capture mechanism in accordance with an embodiment. An artificial chordae device comprises an artificial chordae 1144, a leaflet capture subassembly 1135, and an anchor subassembly 1123. [0046] FIGS. 12 and 13 depict the leaflet capture subassembly 1235 of the artificial chordae, which is composed of an upper jaw 1239, a lower jaw 1240, and a lock feature 1236 to assure proper attachment to the native leaflet. The jaws 1239, 1240 capture the leaflet and have a depth of 2-8 mm, shown as dimension A 1241. In an embodiment, the geometry and the attachment depth of the jaws 1239, 1240 may be designed to prevent damage and unintentional detachment from the native leaflet. The artificial chordae 1244 may be attached to the jaws 1239, 1240 at the tuning mechanism 1242. The artificial chordae 1244 may be attached to a muscle using an anchor subassembly 1223. FIG. 12 depicts the artificial chordae 1244 with the leaflet capture subassembly 1235 in an open configuration.

[0047] FIG. 13 depicts the artificial chordae 1344 with the leaflet capture

subassembly 1335 in a closed configuration. As shown in FIG. 13, the locking mechanism 1336 is engaged. As shown, dimension A 1341 represents the attachment depth of the leaflet capture subassembly 1335 to the native leaflet. In some embodiments, the tension of the artificial chordae 1344 may be adjusted at the tuning mechanism 1342. In some embodiments, the artificial chordae 1344 may be attached to a muscle using an anchor subassembly 1323.

[0048] FIG. 14 depicts an illustrative pulley-based attachment and tuning mechanism in accordance with an embodiment. As shown in FIG. 14, the artificial chordae device 1422 may include a pulley tuning mechanism. In some embodiments, the tuning mechanism may include a pulley 1442 that may be controlled by a torque cable 1446 resident in a delivery catheter. In some embodiments, the torque cable 1446 may be attached to the pulley 1442 via a connection feature 1447. In some embodiments, the leaflet capture assembly 1435 may include a stress relief pad 1438 that enables forces resulting from attachment to the native leaflet 1404 to be distributed. In such embodiments, distributing the attachment forces may prevent damage to the native leaflet 1404 and encapsulate the assembly 1435 after healing. In some embodiments, the artificial chordae 1444 may be attached to the muscle using a barbed anchor subassembly 1423. The artificial chordae 1444 may be tuned so that the artificial chordae replace the operation of the damaged chordae 1406.

[0049] FIG. 15 depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment. As shown in FIG. 15, an artificial chordae device 1522 may include a tuning mechanism that includes a knot 1542. In some embodiments, the knot 1542 may be adjustable and may be used to tune the artificial chordae device 1522 to the correct length. In some embodiments, the knot 1542 may be tuned to the correct length through the delivery catheter 1545. In some embodiments, the knot 1542 may be locked to a final length through movement of a proximal section of a tightening suture 1543. In some embodiments, the artificial chordae device 1522 may be attached to the posterior leaflet 1504 and anchored via a screw- based anchor 1523 to the papillary muscles 1503 to repair the damaged chordae 1506.

[0050] FIG. 16 depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment. As shown in FIG. 16, a plurality of artificial chordae 1644 are implanted in the left ventricle 1602 to properly repair the damaged chordae 1606. In some embodiments, each artificial chordae may be attached to the posterior leaflet 1604 via a suture 1643 and anchored to the myocardium via a screw-based anchor 1623. In some embodiments, the length of each of the artificial chordae 1644 may be adjusted independently by adjusting, for example, the corresponding knot-based tuning mechanism. In some embodiments, adjustments to the tuning mechanism may be performed from the delivery catheter.

[0051] In some embodiments, multiple devices may be attached to the posterior leaflet or the anterior leaflet. In such embodiments, an operator may control the distance between adjacent attachments to leaflet mechanisms. In another embodiment, one or more pads may be used for stress relief of the attachment. In some embodiments, the pads may be large patches that could support a plurality of attachment mechanisms 1638. In alternate embodiments, smaller patches may be used that only support a single mechanism 1638.

[0052] FIG. 17 depicts another illustrative anchor-based attachment and tuning mechanism in accordance with an embodiment. As shown in FIG. 17, artificial chordae 1744 may be implanted to replace damaged chordae 1706 in the left ventricle 1702. In some embodiments, the artificial chordae 1744 may be attached to the posterior leaflet 1704 in pairs on stress relief pads 1738. In some embodiments, the artificial chordae 1744 may be anchored to the myocardium below the papillary muscles 1703. In some embodiments, the tuning mechanism may include one or more torque cables 1746 controlled via the delivery catheter 1745. In some embodiments, a barbed assembly 1723 may be used to anchor the artificial chordae 1744.

[0053] The length of each of the artificial chordae may be from about 20 mm to about 120 mm. For example, the length of an artificial chordae may be tuned to 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 110 mm, 120 mm, or to a length within a range between any two of these endpoints. The variation in the length of the artificial chordae may be used to address variations in ventricle size in a patient population as well as to allow the operator to make a decision as to where to anchor the assembly. For example, different operators may choose to anchor the assembly near to the apex, while other operators may choose to anchor the assembly near to the papillary muscle. Such decisions may be based on the anatomy of the patient and/or operator preference.

[0054] In some embodiments, the design of a chordae replacement device may allow loading the device into a low profile shaft having an outer diameter that is, for example, less than or equal to 13 mm. In some embodiments, the chordae replacement device and the associated delivery system may enable delivery of a plurality of devices, such as the leaflet capture assembly, anchor assembly, and artificial chordae. In some embodiments, the plurality of devices may be delivered consecutively or simultaneously. In some embodiments, the plurality of devices may be housed in parallel inside the catheter prior to delivery. In some embodiments, the plurality of devices may be housed consecutively within the catheter prior to delivery. In some embodiments, only one of the plurality of devices may be loaded into the catheter at a time. In some embodiments, the control mechanism (e.g., the torque cable 1746) may be retained within the catheter.

[0055] The leaflet capture assembly may be configured to attach to the native leaflets of the tricuspid valve or the mitral valve. When used in the mitral position, the leaflet capture assembly may lean in against the edges of the mitral leaflets, anterior or posterior, according to the area that requires treatment. In some embodiments, the attachment mechanism may enable tuning of the tension on the artificial chordae that attaches leaflets to the myocardium. In some embodiments, the attachment mechanism may enable precise positioning with respect to the leaflet. In some embodiments, the attachment mechanism may include a padded surface to distribute the forces and/or to encourage encapsulation of the assembly into the leaflet.

[0056] One of ordinary skill in the art will be aware that any combination of the various components described herein and equivalents may be used for the construction of a particular device based on this disclosure. In other words, the devices depicted herein are merely illustrative of the types of devices that may be constructed according to the teachings of this disclosure and are not meant to be limited to these illustrative embodiments. [0057] FIG. 18 depicts an illustrative anchor subassembly for an artificial chordae in accordance with an embodiment. The anchor assembly 1823 may be configured to attach to the myocardium. In some embodiments, the anchor assembly 1823 may include a self-expanding stent comprising a shape memory material (e.g., Nitinol). In some embodiments, the anchor assembly 1823 may be cut from a tube or sheet and/or use a pattern that allows crimping and expanding. In one embodiment, the anchoring assembly 1823 may be constructed from a wire formed into a coiled geometry configured to be screwed into the tissue. The coiled portion 1824 of the anchor assembly 1823 may be configured to penetrate into tissue and maintain an anchoring force during implantation and in vivo life expectancy.

[0058] In some embodiments, the anchor assembly 1823 may feature an interface portion 1825 that is configured to enable an attachment with a catheter during implantation. The interface portion 1825 may include an attachment 1826 to the delivery catheter that allows transmission of torque forces. The torque forces may be applied to the attachment 1826 to rotate the anchor assembly 1823 and enable the coiled portion 1824 to penetrate into tissue. In some embodiments, axial forces may also be applied to advance the anchor assembly 1823 into or retract the anchor assembly from tissue. In some embodiments, the interface portion 1825 may include one or more holes 1827 configured to attach artificial chordae to the anchor assembly 1823. Illustrative coil-based anchor assemblies are further depicted in FIGS. 10-13, 15, and 16.

[0059] FIG. 19 depicts an illustrative inner member of an anchor subassembly in a deployed configuration in accordance with an embodiment. In some embodiments, an anchor subassembly may include an outer member (depicted in FIG. 21) and an inner member 1928.

The inner member may include a tube having a specific pattern that allows two different configurations as depicted in FIG. 19 and 20. As shown in FIG. 19, a plurality of anchors 1929 may be positioned on a first end of the anchor subassembly 1928. The plurality of anchors 1929 may expand radially to anchor into tissue. In some embodiments, the opposite end 1930 of the anchor subassembly 1928 may provide an interface for attachment to the artificial chordae.

[0060] FIG. 20 depicts the illustrative inner member of the anchor subassembly of FIG. 19 in a non-deployed configuration. As shown in FIG. 20, the anchors 2029 of the anchor subassembly 2028 may be aligned parallel with the interface 2030 of the anchor subassembly. The anchor 2029 may be in the non-deployed configuration when housed within the outer member of the anchor subassembly as discussed further in reference to FIGS. 21 and 22.

[0061] In some embodiments, the inner member of the anchor subassembly may be constructed from one or more metals and/or an alloy. In one embodiment, the inner member is constructed from one or more metals that are biocompatible and are configured to permit the device to transform between the two configurations. For example, the inner member may comprise one or more of cobalt, chrome, stainless steel, or Nitinol.

[0062] FIG. 21 depicts an illustrative outer member of an anchor subassembly in accordance with an embodiment. As shown in FIG. 21, an outer member 2133 of an anchor assembly may comprise a tube with a plurality of windows 2132. In some embodiments, each of the plurality of windows may be located radially. Different window locations are contemplated within the scope of this disclosure. In some embodiments, the outer member 2133 may include a distal portion 2134 having a sharp edge. The sharp edge of the distal portion 2134 may be configured to enable the outer member to penetrate into tissue. In some embodiments, the outer member 2133 may further include a proximal section 2131. In some embodiments, the proximal section 2131 of the outer member 2133 may be used for attachment to the delivery system and/or to the artificial chordae. [0063] In some embodiments, the outer member 2133 of the anchor subassembly may be constructed from one or more metals and/or an alloy. In one embodiment, the outer member 2133 is constructed from one or more metals that are biocompatible. For example, the outer member 2133 may comprise one or more of cobalt, chrome, stainless steel, or Nitinol. In some embodiments, the outer member 2133 may comprise a plastic, such as polyetheretherketone, other materials, or other combinations of materials that are biocompatible.

[0064] FIGS. 22 and 23 depict an illustrative anchor subassembly in a non-deployed configuration 2223 and a deployed configuration 2323, respectively, in accordance with an embodiment. In some embodiments, the inner member 2228/2328 may include a plurality of anchors 2229/2329 and the artificial chordae interface 2230/2330. In some embodiments, the inner member may be inserted into the outer member 2233/2333. In some embodiments, the outer member 2233/2333 may include a plurality of anchor windows 2232/2332, a control interface 2231 to the delivery system, and a distal end 2234/2334.

[0065] In some embodiments, transitioning between the non-deployed configuration and the deployed configuration may be controlled via the delivery catheter by advancing, retracting, and/or rotating the catheter. In some embodiments, transitioning between the two configurations may further be performed with the outer member. For example, linear movement of the inner member 2228/2328 with respect to the outer member 2233/2333 may cause the plurality of anchors 2229/2329 to transition between the two configurations. In some

embodiments, movement of the inner member 2228/2328 may cause the outer member

2233/2333 to deflect the anchors through the windows 2232/2332 mechanically. In some embodiments, the inner member 2228/2328 may be manufactured from a shape memory material, such as Nitinol, and movement of the inner member with respect to the outer member 2233/2333 may cause the anchors to transition to the deployed configuration. In some embodiments, the control interface 2231 may be designed to allow an easy and safe release after the device is anchored to the tissue.

[0066] In some embodiments, the inner member may be manufactured by machining, grinding, and/or laser cutting. In some embodiments, the distal ends 2234/2334 of the anchors 2229/2329 may be sharpened or grinded to enable tissue penetration. In some embodiments, the anchors 2229/2329 may be aligned in a specific direction. In some embodiments, the anchors 2229/2329 may be aligned in two opposing directions. In some embodiments, the anchors

2229/2329 may be aligned in a plurality of directions.

[0067] Any number of anchors 2229/2329 may be used within the scope of this disclosure. In some embodiments, the distal ends 2234 may be inside the corresponding windows 2232 to assure deployment through the windows when the inner member 2228 is within the outer member 2233 in the non-deployed configuration. In some embodiments, the inner member 2228 may be stored within the catheter and advanced into the outer member 2233 separately. In some embodiments, the inner diameter of the outer member 2233 may be in a range of about 0.8 mm to about 4 mm. In some embodiments, the outer diameter of the inner member 2228 may be in a range of about 0.8 mm to about 4 mm, but in any event is less than the inner diameter of the outer member 2233 to allow movement of the inner member therein.

[0068] For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases“at least one” and“one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles“a” or“an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases“one or more” or“at least one” and indefinite articles such as“a” or“an” (for example,“a” and/or“an” should be interpreted to mean“at least one” or“one or more”); the same holds true for the use of definite articles used to introduce claim recitations.

[0069] In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (for example, the bare recitation of“two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to“at least one of A, B, and C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example,“a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, et cetera). In those instances where a convention analogous to“at least one of A, B, or C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example,

“a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, et cetera). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase“A or B” will be understood to include the possibilities of“A” or“B” or“A and B.” [0070] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, et cetera. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, et cetera. As will also be understood by one skilled in the art all language such as“up to,”“at least,” and the like include the number recited and refer to ranges that can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.

[0071] Various of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art, each of which is also intended to be encompassed by the disclosed embodiments.