Patent Application
20190209180
The present disclosure generally relates to thin-film micromesh medical devices and, more particularly, to thin-film micromesh occlusion devices for implantation in the heart.
A septal occlusion device is a medical device used to close an abnormal opening in the wall of the heart (e.g., ventricular septal defects, atrial septal defects, patent ductus arteriosus, patent foramen ovale, or other openings in the wall of the heart).
A left arterial appendage (LAA) occlusion device is a medical device used to seal off the left arterial appendage. As shown in
However, tissue growth on membrane 125 of septal occlusion device 100 or membrane covering 210 of LAA occlusion device 200 may take a long time (e.g. 45 days). Further, tissue growth on membrane 125 or membrane covering 210 may not provide a smooth tissue lining.
An additional advantage of a thin film based septal occlusion device over current devices is the ability to perform a septostomy subsequent to device placement. In certain limited circumstances, for example, in adults with pulmonary arterial hypertension and in pediatric patients with dextro-transposition of the great arteries, it is desirable to form a small hole between the left and right atria using minimally-invasive techniques. Prior treatment of a septal defect with current septal occlusion devices would preclude such a procedure because of the impermeable polymer-based membranes. A sufficiently porous thin film based septal occlusion device, however, would allow for a septostomy procedure post-implantation.
Thus, there is a need for improved occlusion devices for treatment of heart defects and sealing of the LAA.
Embodiments of the present disclosure and their advantages are best understood by referring to the detailed description that follows. It should be appreciated that like reference numerals are used to identify like elements illustrated in one or more of the figures, in which the showings therein are for purposes of illustrating the embodiments and not for purposes of limiting them.
One or more embodiments of the present disclosure provide improved occlusion devices that incorporate a fenestrated thin-film mesh and related methods. The thin-film mesh facilitates incorporation of the occlusion device into the surrounding tissue (e.g., heart tissue or endothelial tissue). More rapid incorporation of the occlusion device into the surrounding tissue may reduce healing time, and improved tissue incorporation may improve the seal formed by the device.
As used herein, a thin-film mesh (also referred to as a thin-film micromesh, a fenestrated thin-film micromesh, or a fenestrated thin-film micromesh sheet) is defined to be less than 100 microns in thickness (e.g., between 2 and 30 microns in thickness). An example thin-film micromesh comprises fenestrated thin-film Nitinol (TFN), although other thin-film micromesh materials may be used to form the occlusion device disclosed herein. The following discussion is thus directed to occlusion devices including thin-film Nitinol without loss of generality. Example fenestrated thin-film Nitinol is disclosed in International Application No. PCT/US2014/61836, filed on Oct. 22, 2014, which claims the benefit of U.S. Provisional Application No. 61/894,826, filed on Oct. 23, 2013 and U.S. Provisional Application No. 61/896,541, filed on Oct. 28, 2013; International Application No. PCT/US2016/039436, filed on Jun. 24, 2016, which claims the benefit of U.S. Provisional Application No. 62/185,513, filed on Jun. 26, 2015, U.S. Provisional Application No. 62/188,218, filed on Jul. 2, 2015, U.S. Provisional Application No. 62/209,185, filed on Aug. 24, 2015, U.S. Provisional Application No. 62/209,254, filed on Aug. 24, 2015, and U.S. Provisional Application No. 62/216,965, filed on Sep. 10, 2015; and International Application No. PCT/US2016/040864, filed on Jul. 1, 2016, which claims the benefit of U.S. Provisional Application No. 62/188,218, filed on Jul. 2, 2015, U.S. Provisional Application No. 62/209,185, filed on Aug. 24, 2015, U.S. Provisional Application No. 62/209,254, filed on Aug. 24, 2015, and U.S. Provisional Application No. 62/216,965, filed on Sep. 10, 2015. The contents of each of these applications are hereby incorporated by reference in their entirety.
To form a thin-film micromesh, Nitinol (NiTi) may be sputtered onto patterned silicon wafers. The patterned mesh may then be removed using a lift-off process by etching away a sacrificial layer such as a chromium layer to form a two-dimensional (2D) thin-film micromesh. A sheet of fenestrated thin-film Nitinol may be disposed about an occlusion device and attached, for example, by soldering, by an adhesive (e.g., glue), by fastening with a wire or string, and/or by stitches. Alternatively, this lift-off process is combined with multiple-layer depositions of Nitinol separated by layers of sacrificial material to fabricate, for example, a hemisphere shaped or cylindrical shaped thin-film micromesh, which are three-dimensional (3D) in the sense that two layers are joined together along their longitudinal edges such that the resulting joined layers may be opened up to form a cylinder.
Thin-film micromesh 325 may be disposed inside wire mesh structure 305 without attachment to wire mesh structure 305. Alternatively, thin-film micromesh 325 is attached to a part of the inner surface of wire mesh structure 305. In one example, thin-film micromesh 325 is attached to wire mesh structure 305 by soldering (e.g., soldering with a low temperature solder), by fastening with a wire or string, by an adhesive (e.g., glue), or by stitches. In other examples, thin-film micromesh 325 is attached to wire mesh structure 305 using other fastening methods as appropriate.
Thin-film micromesh cover 335 may be attached to the outer surface of wire mesh structure 305. Alternatively, or in addition, thin-film micromesh cover 335 may be attached to the inner surface of wire mesh structure 305. In one example, thin-film micromesh cover 335 is attached to wire mesh structure 305 by soldering (e.g., soldering with a low temperature solder), by fastening with a wire or string, by an adhesive (e.g., glue), or by stitches. In other examples, thin-film micromesh cover 335 is attached to wire mesh structure 305 using other fastening methods as appropriate.
In other examples, mesh structure 305 of thin-film micromesh septal occlusion device 300A or 300B of
Thin-film micromesh septal occlusion devices 300A and 300B are shown in their deployed state in
In other examples, frame 405 of LAA occlusion device 400 of
LAA occlusion device 400 is shown in its deployed state in
In one embodiment, a thin-film micromesh such as thin-film micromesh 325, thin-film micromesh cover 335, or thin-film micromesh cover 410 may be formed using a deep-reactive ion etched semiconductor wafer as described International Application Nos. PCT/US2014/61836, PCT/US2016/039436, and International Application No. PCT/US2016/040864, previously referenced herein.
Nitinol may then be deposited on etched wafer 500 to a thickness of approximately 1 to 30 microns (e.g., between 4 and 30 microns, between 4 and 20 microns, between 2 and 20 microns, approximately 10 microns, etc.) and then lifted off. Grooves 505 will then be duplicated on the resulting patterned thin-film Nitinol sheet as corresponding longitudinally-extending fenestrations. The resulting patterns of fenestrations may also be denoted as a fiche in that the fenestrations are in collapsed form prior to an expansion of the Nitinol sheet. Just like a microfiche, each fiche or pattern of fenestrations effectively codes for the resulting fenestrations when the stent cover is expanded to fully open up the fenestrations.
This may be better appreciated with regard to
The resulting high pore density, fenestrations per square mm, (e.g., between 81 and 1075 pores per mm2, between 134 and 227 pores per mm2, between 81 and 227 pores per mm2, etc.) and low metal coverage (e.g., between 19 and 66%, between 24 and 36%, between 19% and 36%, etc.) is very advantageous with regard to promoting a planar deposition of fibrin and a rapid tissue in-growth. In this fashion, the thin-film micromesh is incorporated into the surrounding tissue (e.g., heart tissue or endothelial tissue), which thus seals the abnormal opening or the LAA.
Thin-film micromeshes such as thin-film micromesh 605, orientation of fenestrations, and various parameters for thin-film micromeshes relating to fenestrations such as fenestrations 605, struts such as struts 615, pore density, percent metal coverage, strut angle, and other features of the thin-film micromeshes may be implemented in accordance with the techniques described in International Application Nos. PCT/US2014/61836, PCT/US2016/039436, and International Application No. PCT/US2016/040864, previously referenced herein.
In addition to sealing the abnormal opening or the LAA, the biological seal of the tissue ingrowth also serves to anchor the thin-film micromesh occlusion device (e.g., device 300A, 300B, or 400). As the body incorporates the thin-film Nitinol elements of thin-film occlusion device 200 into the vessel wall, the thin-film occlusion device is stabilized mechanically, thereby mitigating the issue of migration. Notably, this is accomplished without damage to the vessel wall or adjacent structures.
At block 701, a first sacrificial layer (e.g., a lift-off or release layer) of Cr (or other sacrificial or barrier layers) is deposited on a silicon substrate (e.g., silicon wafer substrate 500), for example, in a sputtering chamber while the substrate is held at high vacuum or under ultra-high vacuum, using e-beam evaporation or PECVD. When subsequently etched away, the lift-off layer may release the finished product such as thin-film micromesh 325, 335, or 410 from the substrate (e.g., silicon wafer substrate 500) and may thus be referred to as a release layer. The lift-off layer may be 1700 to 3000 Angstroms of sputter-deposited chromium. Block 701 and one or more of subsequent blocks 702 through 704 may all be performed while the substrate continues to be held under a vacuum in a sputtering chamber and without removing the vacuum (or removing the substrate wafer or device from the vacuum chamber) until all depositions are completed.
Prior to the deposition of the lift-off layer, the substrate may first (e.g., before deposition) be prepared in block 701 by etching (using, for example, dry etching or DRIE) grooves or trenches that will correspond to fenestrations 600 of the web fiche pattern or other surface features that may correspond to structures (e.g., mesh fenestrations) of the finished product.
At block 702, a first layer of NiTi may be deposited using one or more sputtering or other techniques. An example thickness of this first layer (as well as the second layer of NiTi) is between 2 and 30 microns in thickness (e.g., 3 to 5 microns).
At block 703, a second sacrificial layer of Cr (or other sacrificial or barrier layers) may be deposited on the silicon substrate (e.g., silicon wafer substrate 500), for example, in a sputtering (or vacuum) chamber while the substrate continues to be held at high vacuum or under ultra-high vacuum, using e-beam evaporation or PECVD. A shadow mask may be placed over the substrate and the previously deposited layers such as the release layer and the first NiTi layer prior to depositing the second sacrificial layer to protect covered (or blocked) areas from deposition of the second Cr sacrificial layer (or other sacrificial or barrier layers). The shadow mask may be removed from the substrate and the accumulated deposited layers after depositing the second sacrificial layer.
In some embodiments, an aluminum bonding layer is applied using a reverse mask to prevent formation of an oxidized surface layer on the first NiTi layer. It will be appreciated that bonding of one NiTi layer onto another can be problematic if an oxidized surface layer is formed on the first NiTi layer because this surface layer inhibits the bonding of one NiTi layer to another. The reverse mask (as implied by the name) is the complement of the shadow mask used to form the second sacrificial layer. In other words, the reverse mask covers the second sacrificial layer and exposes the uncovered areas of the first NiTi layer. Aluminum may then be sputtered through the reverse mask to form the bonding layer. Since the bonding layer is applied, the first NiTi layer may be exposed to the atmosphere between the masking with the shadow mask and the subsequent masking with the reverse mask. In this fashion, manufacturing costs are lowered in that the applications of the masks is greatly aided by performing the mask applications outside of the vacuum chamber using, for example, conventional semiconductor pick-and-place equipment. Alternatively, the first NiTi layer may be maintained in a vacuum or an ultra-high vacuum until a second layer of NiTi is deposited, including during the application and removal of the shadow mask.
At block 704, a second layer of NiTi may be deposited using one or more sputtering or other techniques. At this block, deposition of the second layer of NiTi may result in the second layer of NiTi bonding to the first layer of NiTi at those areas left exposed by the second sacrificial layer, forming, for example, bonds at the edges of the thin-film micromesh.
In embodiments in which the bonding layer is utilized, wafer 500 may be heated to approximately 500 to 600 degrees prior to removal of the lift-off and sacrificial layers at block 706. Such heating partially melts the aluminum, which then becomes very reactive despite the formation of some aluminum oxides. The molten un-oxidized aluminum is very reactive and chemically bonds to the NiTi layers, resulting in a very secure bond, despite the formation of an oxidized NiTi surface on the first NiTi layer.
At block 705, removal of the sacrificial layers (e.g., the first sacrificial or release layer and the second sacrificial layer) may be performed using a wet etch and may be performed after allowing the vacuum chamber to repressurize or after removing substrate 500 from the vacuum chamber. Etching the sacrificial layers may release the thin-film micromesh from the substrate and may remove interior layers such as the second sacrificial layer. The etch may comprise soaking silicon substrate wafer 500 and the deposited layers in a solution, for example, of Cr etch, and may create a lumen where sacrificial layers are removed between the first and second NiTi layers that are joined at the edges.
At block 706, the thin-film micromesh is expanded such that fenestrations 600 open up into a “chain-link” fence pattern of diamond-shaped fenestrations. Further processing may be performed, such as shaping the thin-film micromesh including, for example, shaping the thin-film micromesh into a more hemisphere shape or cylindrical shape using a mandrel. With the thin-film micromesh in the desired shape, the NiTi layers may be crystallized. Blocks 701-706 are further described in International Application Nos. PCT/US2014/61836, PCT/US2016/039436, and International Application No. PCT/US2016/040864, previously referenced herein.
At block 707, the thin-film micromesh (e.g., thin-film micromesh 325, 335, or 410) is attached or otherwise provided on an occlusion device to form a thin-film micromesh occlusion device (e.g., thin-film micromesh occlusion device 325, 335, or 410). The thin-film occlusion device may then be implanted in a patient using a delivery system.
At block 801, a sacrificial layer (e.g., a lift-off or release layer) of Cr (or other sacrificial or barrier layers) is deposited on a silicon substrate (e.g., silicon wafer substrate 500), for example, in a sputtering chamber while the substrate is held at high vacuum or under ultra-high vacuum, using e-beam evaporation or PECVD. Prior to the deposition of the lift-off layer, the substrate may first (e.g., before deposition) be prepared in block 801 by etching (using, for example, dry etching or DRIE) grooves or trenches that will correspond to fenestrations 600 of the web fiche pattern or other surface features that may correspond to structures (e.g., mesh fenestrations) of a finished product such as thin-film micromesh 325, 335, or 410.
At block 802, a layer of NiTi may be deposited using one or more sputtering or other techniques. An example thickness of this first layer (as well as the second layer of NiTi) is between 2 and 30 microns in thickness (e.g., 3 to 5 microns).
At block 803, removal of the sacrificial layers may be performed using a wet etch and may be performed after allowing the vacuum chamber to repressurize or after removing substrate 500 from the vacuum chamber. Etching the sacrificial layers may release the thin-film micromesh from the substrate. The etch may comprise soaking silicon substrate wafer 500 and the deposited layers in a solution, for example, of Cr etch.
At block 804, the thin-film micromesh is expanded such that fenestrations 600 open up into a “chain-link” fence pattern of diamond-shaped fenestrations. Further processing may be performed, such as shaping the thin-film micromesh including, for example, shaping the thin-film micromesh into a more cylindrical shape by annealing on a mandrel. With the thin-film micromesh in the desired shape, the NiTi layers may be crystallized.
At block 805, the thin-film micromesh (e.g., thin-film micromesh 325, 335, or 410) is attached or otherwise provided on an occlusion device to form a thin-film micromesh occlusion device (e.g., thin-film, micromesh occlusion device 325, 335, or 410). The thin-film occlusion device may then be implanted in a patient using a delivery system.
The thin-film micromesh formed using the techniques described herein is planar with regard to the wire intersections. In that regard, the columnar fenestrations may be expanded into diamond shapes (e.g., having a length of approximately 300 microns and a width of approximately 150 microns). In contrast, the resulting wire forming the diamond-shaped fenestrations is only 2 to 30 microns in thickness. Each “corner” of the diamond-shaped fenestration is thus relatively flat, such that a null region with regard to fluid flow is formed at each corner. This may be better appreciated with regard to
Occlusion devices that include thin-film Nitinol meshes facilitate robust endothelialization and tissue in-growth and, as such, thin-film Nitinol meshes may be advantageously used to improve occlusion devices. A conventional braided stent, a thin-film Nitinol covered stent with a lower pore density, and a thin-film Nitinol covered stent with a higher pore density were tested by implanting in model aneurysms created in rabbits. The animals were then sacrificed after several weeks, and the degree of aneurysm neck healing was examined by removing the arterial vessel segments containing the devices and the model aneurysms for pathological analysis. For the pathological analysis, the arterial vessels were cut along their long axes generating two approximately equal halves, with one half containing the model aneurysm. The sections with the model aneurysm were analyzed with light microscopy. The sections of the devices and micromesh covering the aneurysm neck region were the primary areas of interest.
The aneurysm neck area 920 of the low-pore density thin-film Nitinol covered stent and the aneurysm neck area 930 of the high-pore density thin-film Nitinol covered stent both had robust endothelialization and tissue in-growth compared to the aneurysm neck area 910 of the conventional braided stent. Further, the aneurysm neck area 930 of the high-pore density thin-film Nitinol covered stent had improved endothelialization and tissue in-growth compared to the aneurysm neck area 920 of low-pore density thin-film Nitinol covered stent. Advantageously, thin-film micromesh cover 215 composed of thin-film Nitinol having a pore density of between 50 and 500 pores/mm2 (e.g., between 50 and 250 pores/mm2) will facilitate rapid incorporation of a thin-film incorporated occlusion device such as thin-film occlusion device 200 into surrounding tissue.
Embodiments described herein illustrate but do not limit the disclosure. It should also be understood that numerous modifications and variations are possible in accordance with the principles of the present disclosure. Accordingly, the scope of the disclosure is best defined only by the following claims.
The present application is a continuation application of, and claims the benefit of, International Application No. PCT/US2017/051911, filed on Sep. 15, 2017, which claims the benefit of U.S. Provisional Application No. 62/396,006, filed on Sep. 16, 2016, which are both hereby incorporated by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62396006 | Sep 2016 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2017/051911 | Sep 2017 | US |
| Child | 16357112 | US |
