U.S. patent application number 15/387422 was filed with the patent office on 2017-04-06 for ultra-low fractional area coverage flow diverter for treating aneurysms and vascular diseases.
The applicant listed for this patent is THE REGENTS OF THE UNIVERSITY OF CALIFORNIA. Invention is credited to Gregory P. Carman, Youngjae Chun, Daniel S. Levi, Fernando Vinuela.
Application Number | 20170095357 15/387422 |
Document ID | / |
Family ID | 45004789 |
Filed Date | 2017-04-06 |
United States Patent
Application |
20170095357 |
Kind Code |
A1 |
Carman; Gregory P. ; et
al. |
April 6, 2017 |
ULTRA-LOW FRACTIONAL AREA COVERAGE FLOW DIVERTER FOR TREATING
ANEURYSMS AND VASCULAR DISEASES
Abstract
The various embodiments described herein include methods for
fabricating thin- film flow diversion apparatuses. In one aspect, a
method includes: (1) creating a plurality of trenches using
photolithography and deep reactive ion etching on a substrate; (2)
depositing a metal sacrificial layer on the substrate; (3) forming
a Nitinol layer with a plurality of fenestrations by depositing
Nitinol on the metal sacrificial layer; (4) forming a thin-film of
Nitinol by removing the metal sacrificial layer; (5) crystallizing
the thin-film of Nitinol; and (6) elongating the thin-film of
Nitinol.
Inventors: |
Carman; Gregory P.; (Los
Angeles, CA) ; Levi; Daniel S.; (Pacific Palisades,
CA) ; Chun; Youngjae; (Pittsburgh, PA) ;
Vinuela; Fernando; (Los Angeles, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA |
Oakland |
CA |
US |
|
|
Family ID: |
45004789 |
Appl. No.: |
15/387422 |
Filed: |
December 21, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13668241 |
Nov 3, 2012 |
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15387422 |
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PCT/US2011/037988 |
May 25, 2011 |
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13668241 |
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61348239 |
May 25, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C23C 14/34 20130101;
A61L 31/022 20130101; C23C 14/18 20130101; A61F 2002/068 20130101;
C23C 14/5873 20130101; C23C 16/402 20130101; A61F 2/07 20130101;
C23C 14/185 20130101; A61F 2230/0054 20130101; C23C 14/5806
20130101; C23C 14/345 20130101; A61F 2002/075 20130101; A61F 2/90
20130101; C23C 28/345 20130101; A61L 31/14 20130101; C23C 16/513
20130101; C23C 14/0005 20130101; A61F 2002/823 20130101; C23C
28/321 20130101; C23C 14/30 20130101; A61F 2002/077 20130101 |
International
Class: |
A61F 2/90 20060101
A61F002/90; C23C 28/00 20060101 C23C028/00; C23C 14/58 20060101
C23C014/58; C23C 14/18 20060101 C23C014/18; C23C 16/40 20060101
C23C016/40 |
Goverment Interests
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0004] This invention was made with Government support under Grant
No. W81XWH-07-1-0672, awarded by the ARMY/Medical Research and
Materiel Command. The Government has certain rights in this
invention.
Claims
1. A method for fabricating a thin-film flow diversion apparatus,
comprising: creating a plurality of trenches using photolithography
and deep reactive ion etching on a substrate; depositing a metal
sacrificial layer on the substrate; forming a Nitinol layer with a
plurality of fenestrations by depositing Nitinol on the metal
sacrificial layer; forming a thin-film of Nitinol by removing the
metal sacrificial layer; crystallizing the thin-film of Nitinol;
and elongating the thin-film of Nitinol.
2. The method of claim 1, wherein the substrate comprises a silicon
substrate.
3. The method of claim 1, wherein depositing the metal sacrificial
layer comprises depositing a copper sacrificial layer via e-beam
evaporation.
4. The method of claim 1, further comprising depositing a silicon
dioxide barrier layer by plasma-enhanced chemical vapor deposition
on the metal sacrificial layer prior to the depositing of the
Nitinol.
5. The method of claim 1, wherein the depositing of the Nitinol
comprises depositing the Nitinol by a direct current sputtering
process.
6. The method of claim 1, further comprising generating a
super-hydrophilic surface on the thin-film of Nitinol utilizing
hydrogen peroxide.
7. The method of claim 6, wherein the super-hydrophilic surface has
a water contact angle of less than 5 degrees.
8. The method of claim 6, wherein the super-hydrophilic surface is
configured to deter platelet adhesion at a rate of less than 3
parts per millimeter squared when subjected to platelet rich plasma
for 3 or more hours.
9. The method of claim 1, wherein the Nitinol is deposited via
direct current sputtering.
10. The method of claim 1, wherein the Nitinol is deposited via
hot-target sputter deposition.
11. The method of claim 1, wherein crystallizing the thin-film of
Nitinol comprises heating the thin-film within a vacuum.
12. The method of claim 1, wherein each fenestration of the
plurality of fenestrations has a pore size of less than 500
microns.
13. The method of claim 1, wherein each fenestration of the
plurality of fenestrations has a pore size between 200 microns and
400 microns.
14. The method of claim 1, wherein the thin-film flow diversion
apparatus comprises a thin-film stent cover having a surface
coverage of less than 30%.
15. The method of claim 1, wherein the fenestrations comprise
diamond-shaped apertures.
16. The method of claim 1, wherein the thin-film has a thickness of
less than 12 microns.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a 35 U.S.C. .sctn.111(a) continuation of
PCT international application number PCT/US2011/037988 filed on May
25, 2011, incorporated herein by reference in its entirety, which
is a nonprovisional of U.S. provisional patent application No.
61/348,239, filed on May 25, 2010, incorporated herein by reference
in its entirety. Priority is claimed to each of the foregoing
applications.
[0002] The above-referenced PCT international application was
published as PCT International Publication No. WO 2011/150118 on
Dec. 1, 2011 and republished on Apr. 5, 2012, and is incorporated
herein by reference in its entirety.
[0003] This application is related to PCT International Application
No. PCT/US2010/026430 filed on Mar. 5, 2010, published on Sep. 10,
2010 as PCT International Publication No. WO 2010/102254, and
republished on Jan. 20, 2011, incorporated herein by reference in
its entirety.
INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT
DISC
[0005] Not Applicable
BACKGROUND OF THE INVENTION
[0006] 1. Field of the Invention
[0007] This invention pertains generally to flow diverters, and
more particularly to thin-film flow diverters for treatment of
vascular diseases.
[0008] 2. Description of Related Art
[0009] Conventional stent structures do not provide sufficient flow
diversion to treat aneurysms. Ultra-low porous graft membrane such
as ePTFE or Dacron polyester are too bulky and thrombogenic to be
appropriate for use in the treatment of aneurysms in small vessels
(e.g. vessels less than 5 mm in diameter, including neurovascular
and peripheral arterial circulation) but have been successful in
flow diversion in larger vessels (e.g. abdominal and thoracic
aortic aneurysms).
[0010] PTFE, Dacron and other polymer structures are fabricated in
such a fashion that it is extremely difficult to precisely control
the porosity to a tolerance of 1 micron. Even in cases where
porosity can macroscopically be controlled in these materials,
specific shapes and distributions cannot be generated precisely.
For example, it is highly difficult, if not impossible, to
specifically fabricate a circular or diamond shape pattern that is
regular and repeating into structures comprising these materials.
In addition, ePTFE and Dacron are also very thick relative to thin
films (on the order of 100 microns thick). This increases the size
of any flow diversion device without providing significant benefit
in regards to the thickness direction.
[0011] In many flow diverter applications, complete occlusion of
the vessel's anomaly is unnecessary, and only partial occlusion is
generally desired or warranted. Previous teachings of using
deployable stents indicate for neurovascular applications the
coverage area of the aneurysm sac must be at least 30%. These
studies use large size holes (relative to the dimension of blood
products) for evaluation.
[0012] Current approaches to prevent aneurysms from rupturing
include both surgical and transcatheter methods. A surgical
approach to treat aneurysms by "clipping" the aneurysm neck was
developed by Dandy in 1936 and proved to be an effective treatment
for a select group of aneurysms. However, this procedure requires a
craniotomy (an opening in the skull) and is not always applicable
depending on the aneurysm size, location, and complexity.
[0013] More recently, transcatheter procedures to treat vascular
aneurysms have been developed. An endovascular therapy using
platinum coils to fill the aneurysm sac was introduced in 1990.
Because this coil embolization technique is less invasive and more
cost effective than surgery, it has become the standard of care for
most aneurysms. These coils pack the aneurysm sac densely to limit
blood flow in the aneurysm and produce more local thrombosis within
the aneurysm. While coils are beneficial, they can only be used for
aneurysms with "necks" narrow enough to hold coils in the aneurysm.
To address this issue, a stent can be placed across the neck of a
broad-neck aneurysm and coils placed into the aneurysm through the
cells of the stent. This procedure is complicated (it involves two
types of devices: a stent and multiple coils), sometimes does not
produce aneurysm occlusion, and is limited by the physical size of
the stent's delivery system. The ideal device for treatment of
aneurysms would be a "covered" stent, which occludes the neck of
both narrow and broad necked aneurysms.
[0014] "Covered stents" have traditionally been conventional mesh
type stents wrapped in expanded polytetrafluoroethylene (ePTFE).
While they can wall off aneurysms by circumferentially covering the
wall of an artery, they have been far too bulky for use as
neurovascular stents or in other flow diversion vascular systems
requiring a low profile. A low profile covered stent for the
treatment of aneurysms in small, tortuous vessels has yet to be
fully evaluated in vivo or in vitro.
[0015] Therefore, an object of the present invention is production
and use of a thin-film structure (e.g. 1-10 microns) that can be
patterned with specific shapes with a relatively high tolerance
level (e.g. 1 micron or less).
[0016] Another object is to decrease the percent coverage of the
material deployed over an aneurism sac by reducing the size of the
fenestration.
[0017] A further object is a thin-film manufacturing process to
enable a wide range of different shapes and distributions to be
manufactured onto a single vascular flow diverter.
[0018] Another object is to provide a surface treatment to the
thin-film that produces a rapid clotting cascade preventing flow
into the aneurysm sac. At least some of these objectives will be
met in the description provided below.
BRIEF SUMMARY OF THE INVENTION
[0019] An aspect of the present invention is patterning of thin
films, and in particular construction of vascular flow diversion
devices for various vascular diseases including but not limited to
treating aneurysms and other applications. The devices of the
present invention are configured to be extremely low profile and
are covered with the minimal amount of blood contacting material.
The thin-film manufacturing processes of the present invention
allow for production of ultra-low profile and hyperelastic
structures (e.g. >400% elongation). These hyperelastic
properties allows for the creation of self expanding vascular flow
diversion devices, and in particular delivery of the material on a
self expanding platform without folding of the material. In vitro
and in vivo experiments show flow diversion devices manufactured
with the micro-machined thin-film of the present invention, along
with a stent or support structure, do not generate thrombosis in
the arteries less than 5 mm and provide adequate and rapid flow
diversion without production of intimal hyperplasia or vascular
stenosis.
[0020] Simulated blood studies have shown that the thin-film
structures of the present invention are capable of reducing the
intra-aneurismal flow velocity and vorticity greater than 90% in a
pseudo-aneurysm, even though the coverage area was less than
.about.10%.
[0021] In-vitro flow studies of the thin-film structures of the
present invention using human whole blood shows an occlusion of a
pseudo-aneurism within approximately 15-30 minutes using a 200
micron fenestration (i.e. 300 micron as fabricated). Occlusion
occurred due to the deposition of blood products such as fibrin
scaffolds on the mesh structure.
[0022] In animal studies, micro-machined thin-film flow diverters
with 200 microns fenestrations (i.e. 300 microns as fabricated)
were demonstrated to occlude surgically created aneurysms in less
than 5 minutes. Flow diversion devices with 400 micron
fenestrations (i.e. 500 microns as fabricated) occluded broad
necked aneurysm within less than an hour.
[0023] Given the overall porosity and sparse coverage (.about.10%
coverage), the rapid flow diversion seen with the devices of the
present invention in the lab and in animals represents a paradigm
shift in future flow diverter technology. The physical size of the
fenestration and surface treatment are of utmost importance, even
with low density of coverage. General convention in the existing
art is that is would not be possible to so quickly occlude an
aneurysm sac without using a more complete covering (e.g.
>40-50% coverage).
[0024] Test results show that the size of the fenestration (e.g.
200 micron size and 300 micron as fabricated) as well as surface
treatment may be critical for proper function within a particular
size vessel and flow conditions. Depending on the application (e.g.
the size and flow dynamics of the parent artery), fenestrations in
a particular range will immediately produce the formation of fibrin
structures due to the flow disruptions imposed by the ultra-fine
size fenestrations. Such an affect has not been previously shown
nor contemplated by those skilled in the art. While the systems and
methods of the present invention present a major breakthrough for
treating brain aneurysms, the methods and systems of the present
invention may be configured for use in a wide range of applications
where flow diversion is desired.
[0025] Further aspects of the invention will be brought out in the
following portions of the specification, wherein the detailed
description is for the purpose of fully disclosing preferred
embodiments of the invention without placing limitations
thereon.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)
[0026] The invention will be more fully understood by reference to
the following drawings which are for illustrative purposes
only:
[0027] FIG. 1 shows a schematic diagram of ultra-low profile
micropatterned thin-film Nitinol flow diverter placed in the
small/broad-neck aneurysm site.
[0028] FIG. 2 illustrates a heart having an Atrial Septal Defect
(ASD).
[0029] FIG. 3 shows a flow diverter assembly installed in a
location within a patient's heart to treat an Atrial Septal Defect
(ASD).
[0030] FIGS. 4A through 4H show images of thin-film flow diverters
of the present invention having various sizes and shapes of
patterns fabricated with a lift-off microfabrication process.
[0031] FIG. 5A shows an image of a 150 micron diamond-patterned
thin-film flow diverter prior to elongation.
[0032] FIG. 5B shows an image of a 150 micron diamond-patterned
thin-film flow diverter after elongation.
[0033] FIG. 6A shows an image of a 300 micron diamond-patterned
thin-film flow diverter prior to elongation.
[0034] FIG. 6B shows an image of a 300 micron diamond-patterned
thin-film flow diverter after elongation.
[0035] FIG. 7A shows an image of a 500 micron diamond-patterned
thin-film flow diverter prior to elongation.
[0036] FIG. 7B shows an image of a 500 micron diamond-patterned
thin-film flow diverter after elongation.
[0037] FIGS. 8A through 8D show images of thin-film flow diverters
of the present invention having various sized circular or
elliptical shaped patterns.
[0038] FIG. 9 shows an image of a stent assembly having an
ultra-low profile fractional area coverage flow diverter using
micropatterned thin-film Nitinol.
[0039] FIGS. 10A and 10B show two views of a flow diverter
comprising a hyper-elastic, high-porous thin film disposed over a
Neuroform stent.
[0040] FIGS. 11A and 11B show two views of a flow diverter
comprising a hyper-elastic, high-porous thin-film disposed over a
pfm stent.
[0041] FIG. 12A illustrates a flow velocity profile of an aneurism
without any flow diversion.
[0042] FIG. 12B illustrates a flow velocity profile of an aneurism
without a present-art flow diverter installed.
[0043] FIG. 12C illustrates a flow velocity profile of an aneurism
with an ultra-low profile micropatterned thin-film Nitinol flow
diverter of the present invention installed.
[0044] FIGS. 13A and 13B show plots of interaneurismal flow. FIG.
13A shows the percent reduction in flow velocity in wide neck
aneurism sac. FIG. 13B shows the percent reduction in flow velocity
in fusiform aneurism.
[0045] FIGS. 14A through 14C show flow diverters of the present
invention installed within different aneurism types (small neck:
FIG. 14A; wide neck: FIG. 14B; and fusiform: FIG. 14C) of in vitro
models with human whole blood
[0046] FIGS. 15A and 15B show photographs of different views of
fibrin deposition of an in vitro fusiform model using whole blood
after 30 minutes.
[0047] FIG. 16 shows an SEM image of fibrin deposition of in vitro
fusiform model using whole blood after 30 minutes.
[0048] FIG. 17 shows a zoomed-in image of the left side of the SEM
image of FIG. 16.
[0049] FIG. 18A image of angiogram showing a surgically place
aneurism in the carotid artery of a swine.
[0050] FIG. 18B illustrates an angiogram of the same vessel of FIG.
18A immediately (<5 minutes) after deployment of the device of
the present.
[0051] FIG. 19 is a photograph of the harvested aneurysm sac of
FIGS. 18A and 18B approximately 2 hours after angiogram of FIG.
18B.
[0052] FIG. 20 is an SEM image of the harvested aneurysm sac of
FIG. 19, showing complete fibrin deposition of the implant.
[0053] FIG. 21 illustrates an exemplary treatment method for
generating a super hydrophilic thin film NiTi surface.
[0054] FIG. 22 is a flow diagram of a pretreatment dip used in the
method of FIG. 21.
DETAILED DESCRIPTION OF THE INVENTION
[0055] FIG. 1 shows a schematic diagram of ultra-low profile
micro-patterned thin-film flow diverter 10 placed in the
small/broad-neck aneurysm site 12 of vessel 14. Vessel 14 generally
has flow F.sub.A traveling in the direction from upstream end 16 of
the aneurism site 12 to downstream end 18.
[0056] The flow diverter 10 generally comprises a micro-patterned
thin-film Nitinol (representing a generic composition of NiTi)
sheet 30 disposed over a collapsible stent 20 comprised of a
plurality of connected members 22. In one embodiment, the thin-film
sheet 30 may comprise diamond shaped holes on the order of 200
microns when deployed (300 microns as fabricated), and with and a
percentage coverage area on the order of .about.10% solid.
[0057] It may also be possible to deliver micro-patterned thin-film
Nitinol sheet 30 (or other biocompatible material) to the neck of
aneurysms with other devices, (i.e. devices other than commercially
available stents). Because thin film structure 30 utilizes
micro-fabrication processes coupled with thin-film metals to
manufacture very small pore sizes (e.g. .about.1-400 microns), it
is not limited by the availability of either the wire mesh density
or macroscopic structures that would not provide the flexibility,
the physical dimensions, or the physical geometries required to
both limit flow while also providing a sparse coverage.
[0058] While the present description focuses on a single layer of
film 30 containing an array of perforations or holes, it is
contemplated that the flow diverter 10 may also comprise a multiple
layers film, each containing a wide range of holes.
[0059] Thin-film 30 may also configured to be "hyper-elastic," such
that it elongates greater than 100% without permanent deformation.
While this hyperelasticity is not is not necessary for flow
diversion, it is advantageous for attaching film to a
self-expanding device (e.g. stent 20) that can be collapsed into a
small catheter and delivered in a transcatheter fashion.
[0060] The efficacy of the thin-film flow diverter 30 has been
demonstrated both in vitro and in vivo, as will be shown in the
description below. Thin-film flow diverter 30 is configured to be
easily mounted onto a variety of scaffolds or structures, including
stents (e.g. such as stent 20 shown in FIG. 1), and woven metallic
structures, as well as other collapsible devices available in the
art.
[0061] The particular example shown in FIG. 1 and throughout the
foregoing disclosure comprises an ultra-low profile flow diversion
device for neurovascular aneurysm treatment. However, it is
contemplated that the flow diverter 10 may be configured as a
device designed for flow diversion from a diversity of vascular
imperfections, including thoracic and abdominal aortic aneurysms,
pseudo-aneurysms, peripheral aneurysms, etc. Although most
aneurysms are found in the brain, device 10 may function as a flow
diverter for peripheral aneurysms such as those found in the
splenic artery and renal arteries.
[0062] In addition to being used for aneurysm occlusion, the device
of the present invention may be used to provide the flow diversion
for occlusion of unwanted fistulas, including but not limited to
ASDs (atrial septal defects), VSDs (ventricular septal defects
allowing mixing of blood from left and right ventricles), occlusion
of the LAA (left atrial appendage, to prevent blood clot formation
in atrial fibrillation), and PDAs (patent ductus arteriosus, a
fistula between the aorta and pulmonary artery). Generally, these
unwanted cardiac communications have also been classically treated
with transcatheter devices. Although these lesions are very high
flow and often have high pressure gradients across them, these
lesions may be treated by providing occlusion with a modified
version of thin-film 30.
[0063] FIG. 2 illustrates a diagram of a heart 40 having an Atrial
Septal Defect (ASD) 48 within the atrial wall 46. Defect 48
generally comprises a perforation in the heart wall 46 that allows
problematic blood flow 50 from in between the right atrium 44 and
left atrium 42 allowing mixing of blood from left and right
atria.
[0064] FIG. 3 shows an exemplary flow diverter assembly 60
installed in a location within a patient's heart to treat an Atrial
Septal Defect (ASD) 48. The device 60 generally comprises
micropatterned thin-film Nitinol sheets 62 supported by support
structures 64 and 66. Support structures 64 and 66 are configured
to enclose left and right sides of the fistula 48 in atrial wall 46
via central member 68 that passes through the perforation 48. The
thin-film sheets 62, while perforated, are configured (and/or
potentially surface treated) to promote fibrin deposition within
the lattice network of perforations to occlude flow between the
fistula 48.
[0065] FIGS. 4A through 4H show images of thin-film flow diverters
of the present invention having various sizes and shapes of
patterns fabricated with the lift-off microfabrication process
described in further detail below.
[0066] FIG. 4A shows a SEM image of a thin-film sheet 70 having a
pattern of 5 micron circular fenestrations or holes 72. This thin
film sheet can be from a wide range of Nitinol compositions
(including ternary compositions) as well as from the general class
of metals including Ti. FIG. 4B shows a SEM image of a thin-film
sheet 74 having a pattern of 20.times.10 micron elliptical holes
76. FIG. 4C shows a SEM image of a thin-film sheet 78 having a
pattern of 105.times.75 micron elliptical holes 80. FIG. 4D is a
SEM image of a thin-film sheet 82 having a pattern of 40.times.30
micron diamond holes 84. FIG. 4E shows a SEM image of a thin-film
sheet 86 having a pattern of 100.times.50 micron ellipse 88 and
connected ellipse 90 fenestrations. FIG. 4F shows a SEM image of a
thin-film sheet 92 having a pattern of 180.times.60 micron
connected ellipse fenestrations 94 and 96. FIG. 4G is a SEM image
of a thin-film sheet 100 having a pattern of 20.times.20 micron
rectangular holes 102. FIG. 4H is a SEM image of a thin-film sheet
104 having a pattern of 150 micron diamond holes 106.
[0067] FIGS. 5A through 7B show images of hyper-elastic thin-film
flow diverters of the present invention having various shaped
patterns fabricated with the lift-off microfabrication process.
[0068] FIG. 5A shows an image of a thin-film flow diverter 108 with
150 micron diamond-shaped fenestrations 110 prior to elongation.
FIG. 5B shows the 150 micron diamond-patterned thin-film flow
diverter 108 of FIG. 5A after elongation.
[0069] FIG. 6A shows an image of a thin-film flow diverter 116 with
300 micron diamond-shaped fenestrations 118 prior to elongation.
FIG. 6B shows the 300 micron diamond-patterned thin-film flow
diverter 116 of FIG. 6A after elongation.
[0070] FIG. 7A shows an image of a thin-film flow diverter 120 with
500 micron diamond-shaped fenestrations 122 prior to elongation.
FIG. 7B shows the 500 micron diamond-patterned thin-film flow
diverter 120 of FIG. 7A after elongation.
[0071] FIGS. 8A through 8D show images of thin-film flow diverters
of the present invention having patterns fabricated with the
lift-off microfabrication process that have rounded edges, such as
circular and elliptical fenestrations. FIG. 8A shows an image of a
thin-film flow diverter 124 with 20 micron circular fenestrations
126. FIG. 8B shows an image of a thin-film flow diverter 128 with
40 micron circular fenestrations 130. FIG. 8C shows an image of a
thin-film flow diverter 132 with 80 micron circular fenestrations
134. FIG. 8D shows an image of a thin-film flow diverter 136 with
60.times.20 micron elliptical fenestrations 138.
[0072] FIGS. 10A through 11B show flow diverters comprising
hyper-elastic, high-porous film disposed over separate stents.
FIGS. 10A and 10B show two views of a flow diverter 160 comprising
a hyper-elastic, high-porous thin film 160 disposed over a
Neuroform stent 164. FIGS. 11A and 11B show two views of a flow
diverter 170 comprising a hyper-elastic, high-porous thin-film 172
disposed over a pfm stent 174.
[0073] Contrary to conventional wisdom, the extremely small
diameter fenestrations shown in the various thin films of the
present invention depicted in FIGS. 4A through 8D are extremely
effective flow diverters, despite their low surface coverage. Flow
diversion tests are shown and discussed below for the thin films of
FIGS. 5A, 5B, 6A, 6B, 7A and 7B. The change in size of the
fenestrations from the fabricated state to the deployed state is
illustrated in these figures. In addition, other flow diverter
sizes and shapes have been fabricated as illustrated in FIGS. 4A
through 8D.
[0074] The micro-machined Nitinol thin-film 30 of the present
invention allows for the production of devices which only require
5-20% surface coverage, compared to existing devices that require
greater than 30% coverage. Coverage area is defines as percent
coverage of the structure (e.g. 100% coverage would be a solid
material). Similar strategies could also be used with thin films
created from a variety of other metals and organic and inorganic
substrates. It is typically believed that surface coverage of
greater than 30% is required to adequately quiesce a neurovascular
aneurysm. Current teachings in the art suggest that flow diverters
with less than 30% coverage are ineffective in many applications
such as a brain aneurysm (see Satoshi Tateshima et al., Alteration
of intraaneurysmal hemodynamis by placement of a self-expandable
stent, J Neurosurg, 111:pp. 22-27, 2009.)
[0075] However, constructing such devices with less surface
coverage allows for the production of less thrombogenic devices
which are less likely to occlude the parent or perforating vessels.
Combining low surface coverage with thin films also allows for the
production of flow diversion devices with an unprecedented low
profile. This is extremely important for certain vascular regions
in the body such as intercranial applications.
[0076] The thin-film 30, having surface coverage less than 15%,
creates rapid thrombosis within the aneurysm sac 12, thus
preventing possible ruptures with minimal coverage of the vessel
wall 14. Accordingly, device 10 reduces the chance that the parent
vessel will be occluded by thrombus, and decreases the chances of
occluding vital perforating arteries in close proximity to the
aneurysm being treated. Furthermore, since substantially smaller
amounts of material are used in the device 10, the size of the
delivery system will also be reduced.
[0077] Fabrication of Micro Machined Thin-Film Nitinol Sheets and
Flow Diverters
[0078] All the fabricated films shown in FIGS. 4A-8D contained
holes or fenestrations which extended through the entire thickness
of the film. Generally, the thickness of the thin films preferably
ranges between about 2 .mu.m and about 12 .mu.m, and more
preferably between about 6 .mu.m and about 8 .mu.m. For many
transcatheter applications, it is also desirable to have the
fabricated films to be extremely flexible. To achieve large
strains, both phase transformation and structural issues were
considered as well as the types of holes fabricated. Structural
behaviors of specific hole shapes were first investigated to find
design patterns that produced hyper-elastic strain with minimal
buckling. Four different configurations were used that accommodate
strains ranging between 100-800% without failure, and are shown in
FIGS. 5A through 7B and 10A through 11B. This elongation itself
represents a major advancement, since most currently produced
metallic or Nitinol structures can only produce approximately 10%
elongation or less.
[0079] While highly beneficial in certain applications, it is
appreciated that the hyper-elastic component is not necessary for
the flow diverter 10 of the present invention. The flow diverter 10
may be combined with other properties that are amenable
specifically for all transcatheter applications. For example, in
the treatment of brain aneurysms, it may be beneficial for the flow
diverter 10 to have maximum elasticity so that it may be collapsed
into a very small diameter catheter and subsequently deployed into
a very large diameter vessel. Therefore, in this particular example
hyperelasticity combined with a flow diverter is a desirable
attribute.
[0080] The thin films shown in FIGS. 4A through 8B and 10A through
11B were fabricated by hot-target sputter deposition in combination
with a lift-off micro machining method of the present invention.
This lift-off method creates trenches on the Si substrate using
photolithography and dry etching technique. The first step in the
lift-off method for producing porous thin-film Nitinol is to create
50 .mu.m deep trenches using conventional photolithography and deep
reactive ion etching (DRIE) technique. Following this, 500 nm Cu
sacrificial layer and 500 nm SiO.sub.2 barrier layer deposited by
e-beam evaporation and PECVD techniques, respectively. The
thin-film Nitinol is deposited by DC sputtering process onto the
SiO.sub.2. Cu and SiO.sub.2layers are removed and stand alone film
is crystallized at 500.degree. C. for 120 minutes in a vacuum of
less than 1.times.10.sup.-7 torr. The fabricated porous thin-film
Nitinol confirms the material superelastic properties at
36.5.degree. C.
[0081] FIG. 9 shows an image of a stent assembly 150 having an
ultra-low profile fractional area coverage flow diverter using
micropatterned thin-film Nitinol sheet 152 over stent 154.
[0082] The 6 .mu.m thick micropatterned Nitinol thin-film sheet 152
is covered over commercially available neurovascular and peripheral
stent 154 and is adhered using either polymer adhesive, laser
welding or suturing. Other micromechanical devices may also be used
to adhere thin films to stents or other structures designed to
deploy patterned thin films as flow diversion devices. Commercially
available 3.5 mm and 4 mm neurovascular stents as well as 6 mm
self-expanding stents intended for peripheral use were used with
micropatterned thin films for laboratory and animal testing.
[0083] In order to minimize any possible thrombosis in the parent
artery, super-hydrophilic surface treatments (such as that provided
in PCT International Application No. PCT/US2010/026430 filed on
Mar. 5, 2010, published on Sep. 10, 2010 as PCT International
Publication No. WO 2010/102254, and republished on Jan. 20, 2011)
may preferably be performed prior to or following attachment of the
film.
[0084] FIG. 21 illustrates an exemplary treatment method 200 for
generating a super hydrophilic thin film NiTi surface in accordance
with the present invention. A thin film NiTi sheet is generated
using a DC sputter deposition technique as follows: A near
equiatomic NiTi alloy target is placed under UHV (ultra-high
vacuum) atmosphere. The base pressure of the sputter chamber is set
below 5.times.10.sup.-8Torr and the Ar pressure was
1.5.times.10.sup.-3Torr. A 4'' silicon wafer is used as a substrate
with a 5000 .ANG. thick silicon dioxide layer. To minimize
compositional variations, the wafer is translated in 80 mm lengths
perpendicular to the heated NiTi target. Films (i.e., 6 .mu.m
thick) are fabricated with a deposition rate of 0.1 .mu.m/min.
Following deposition, the film is mechanically removed from the
wafer and crystallized at 500.degree. C. for 120 minutes in a
vacuum less than 10.sup.-7 Torr.
[0085] The thin film is first pretreated according to steps 202,
204, and 206. In one embodiment shown in FIG. 22, a cleaning
pretreatment dip 202 comprises sequentially dipping the film in
acetone at 214, methanol at 216, and finally alcohol at 218 for 5
minutes. At step 204, the film is subsequently placed in a buffered
oxide etchant (BOE: aqueous NH.sub.4-HF etchant) to eliminate the
native oxide layer. Next, the film undergoes passivation in a
nitric acid (HNO.sub.3) solution (e.g. 30%) for 40 min at step 206.
It is appreciated that while the above steps may be optimal for
pretreating the film, one or more of the above pretreatment steps
may be modified or omitted. For example, the total pretreatment
process may simply comprise the passivation step 206.
[0086] At step 208, the thin film NiTi is then surface treated
using a hydrogen peroxide treatment which comprises placing the
film in a concentration of hydrogen peroxide (H.sub.2O.sub.2)
solution mixed with deionized water at a specified temperature for
a specified period of time. It is appreciated that the ideal
treatment (e.g. for creating a super hydrophilic surface) is a
function of the concentration of H.sub.2O.sub.2, time, and
temperature (e.g. HPT.sub.d,f,g, where d=H.sub.2O.sub.2
concentration, e.g. 3-30%, f=temperature, e.g. 25.degree. C. or
110.degree. C., and g=time, e.g. 0.5.about.15 hrs). For example, a
super hydrophilic surface may be achieved by immersion of thin film
NiTi in a H.sub.2O.sub.2 concentration of 30% at 25.degree. C. for
15 hours. It is appreciated that in an increased temperature, e.g.
boiling at 110.degree. C., and/or concentration percentage, may
result in a super hydrophilic surface being achieved in less
time.
[0087] At step 210, the film is then removed from the
H.sub.2O.sub.2 solution, and then stored in a high humidity
environment at step 212. Step 212 is configured to maintain the
surface condition of the super hydrophilic surface generated from
the treatment step 208 without decaying of hydrophilicity. In one
embodiment, step 212 comprises fully immersing the film in a
deionized water (DI) solution. Alternatively, the film may be
contained in high humidity air (e.g. >90% humidity) via a
humidifying element, humidor, or the like.
[0088] Storage of the film in a high humidity environment, as
detailed above in treatment method 200, aids in preventing the
release of the hydroxyl groups. While reducing the wetting angle,
the hydroxyl groups bound to the surface are unstable and are
easily be decomposed in ambient air environment. By storing the
surface treated thin film in a high humidity environment (e.g. step
212), decay of super hydrophilicity is prevented. In one
embodiment, step 212 comprises placing a fully saturated deionized
(DI) water cloth in a vacuum bagged container along with the
treated thin film. The thin film may be coiled inside a catheter
for ready installation for a desired procedure. While the above
preservation approach may be the most practical, it is contemplated
that other preservation/hydration processes may also be
employed.
[0089] Generally, the super-hydrophilic surface will a water
contact angle of less than approximately 5 degrees, and/or be
configured to deter platelet adhesion at a rate of less than 3
parts per mm.sup.2 when subjected to platelet rich plasma for 3 or
more hours. As detailed below, experimental results found thin film
Nitinol sheets having this surface treatment act as a beneficial
source for fibrin deposition to promote rapid occlusion of the
desired region, in this example an aneurysm sac. Such results are
unexpected, as conventional understanding would generally lead one
skilled in the art to expect that a surface highly effective in
deterring platelet adhesion would also deter fibrin deposition.
However, the process above for generating a super-hydrophylic
surface results in a significantly increased oxide layer (TiO)
having negatively charged hydroxyl groups. It is believed that
these negatively charged ions attract the positively charged
fibrin, thus resulting in rapid fibrin deposition and
occlusion.
[0090] Currently, the flow diverter manufactured with
micropatterned thin-film Nitinol can be collapsed into 3 Fr
catheter when mounted onto neurovascular Neuroform stents from
Boston Scientific. It is anticipated that this device will be able
to be collapsed into and delivered by catheters even less than 3
Fr.
[0091] Based on the above models, small scale features can be
produced in thin films Nitinol or of other metals. As detailed
above, photolithography is used to produce physical features as
small as a couple of microns. It should be noted that e-beam
lithography may also be used to produce features as small as 5
nanometers. Therefore, the thin films of the present invention are
not limited to feature sizes above 1 micron (see film 100 in FIG.
4G for 20 micron size patterns and film 70 in FIG. 4A for 5 micron
sizes produced). When the porosity of physical feature decreases
(e.g. smaller diameter holes), the line area around the feature
divided by the total area increases. Therefore, as the feature size
decreases this ratio increases. This is of vital importance because
at the perimeter of the physical feature (e.g. circumference of the
hole) there is a zero flow condition. Thus, as the ratio increases,
even though the total porosity remains a constant, the net flow
through the flow diverter will dramatically decrease.
[0092] By appropriately configuring the structure (e.g. this cannot
currently be done with woven systems) the flow pattern can be
further decreased. This can be achieved by introducing sharp
corners as one example where flow stagnation is known to occur, as
well as fabricating a specific shape relative to the flow velocity
to produce stagnation. By making the physical dimensions of the
pores on the order of blood products (e.g. red blood cells are 5-10
microns), the flow diverter 10 actually prevents flow and begins to
act as a sieve that becomes clogged to prevent flow. Note, the
latter can actually be achieved with nearly 0% coverage area. Even
though the size of the holes is larger than blood products (e.g.
holes on the order of 200 microns) they promote the almost
immediate formation of fibrin depending upon the flow conditions,
which can lead to an almost immediate cessation of flow. Thus, the
above three physical features, coupled with one biological
interaction, contribute to flow diversion in small scale structures
that can be produced in a thin-film metal.
[0093] The thin-film Nitinol flow diversion device 10 of the
present invention may be used for treatment of any small vessel
aneurysm (aneurysms in vessels <6 mm) as well as many other flow
diverters in the vascular system. The thin films of the present
invention are compatible with even the most remote and wide-necked
neurovascular aneurysms, as well as a wide range of other
applications in larger vessels and even for intracardiac
structures. Thus, the device is specifically amenable to the
treatment of brain aneurysms:
[0094] (a) Delivery by transcatheter fashion in a delivery sheath
less than or equal to 3 Fr (4 Fr delivery sheathes would be
acceptable for larger 5 and 6 mm vessels harboring more proximal
aneurysms);
[0095] (b) Delivery performed using standard neurovascular
techniques, equipment and standards that have already been
developed for delivery of commercially available stents to the
necks of aneurysms'
[0096] (c) Sufficient flexibility to reach even small cranial
vessels distal to the Circle of Willis;
[0097] (d) Ability to cause acute thrombus of aneurysms without
significant effects on the parent vessel or on perforators.
Preferably the porosity physical dimensions will be less than or
equal to 400 microns and the percent coverage will be less than
20%.
[0098] Experimental Results
[0099] Referring now to FIGS. 12A through 14C, the efficacy of a
flow diverter in accordance with the present invention having small
pore size and small fractional coverage, was experimentally
demonstrated.
[0100] FIG. 12A illustrates a flow velocity profile of an aneurism
12 without any flow diversion. The flow F.sub.A in the artery 14 is
generally subject to diverted flow F.sub.I in and F.sub.O out of
the aneurism 12. FIG. 12B illustrates the flow velocity profile of
an aneurism 12 without a presently available flow diverter
installed. As shown in FIG. 12B, the flow in F.sub.I is reduced by
66.5% and flow out F.sub.O is reduced by 68%.
[0101] FIG. 12C illustrates a flow velocity profile of an aneurism
with an ultra-low profile micropatterned thin-film Nitinol flow
diverter of the present invention installed. As shown in FIG. 12C,
the flow in F.sub.I is reduced by 96% and flow out F.sub.O is
reduced by 97.8%.
[0102] FIGS. 14A through 14C show a test to evaluate a flow
diverter 10 in reducing flow in a simulated wide neck 12B or
fusiform 12C aneurysm sac created from a plastic and/or glass mold
14. The size of the neck for both of these aneurysms was 8 mm and
the diameter of the simulated vessel 14 was 4 mm. The flow
conditions were stenotic. In these studies both 300 micron size
(FIGS. 6A,B) and 500 micron size (FIGS. 7A,B) thin films were used
on the device to evaluate the reduction of flow velocity into the
aneurysm sac. It should be noted that when the flow diverter 10 is
deployed into the simulated vessel 14, the representative total
coverage area of the neck (12A-C) is less than 15%, as can be seen
in the magnified images of diverter 160 shown in FIGS. 10A and 10B.
In these tests, flow reductions on the order of greater than 90%
compared to the sac without a flow diverter were achieved.
[0103] The largest flow reduction was achieved with the 300 micron
size fenestrations 118 of the thin film 116 shown in FIGS. 6A and
6B. It should also be noted that in all of these tests the film had
been treated with the super-hydrophilic surface treatment described
above. The sparse coverage (as little as 10% or less) with small
pore size (200 micron size pores of the fenestrated 5 micron thick
thin-film 116) were found to significantly reduce (>90%) the
intra-aneurismal flow velocity and vorticity.
[0104] FIG. 13A shows the percent reduction in flow velocity in
wide neck aneurism sac 12b with 500 micron (FIGS. 7A,B) and 300
micron (FIGS. 6A,B) thin films installed. FIG. 13B shows the
percent reduction in flow velocity in fusiform aneurism 12c with
500 micron (FIGS. 7A,B) and 300 micron (FIGS. 6A,B) thin films
installed.
[0105] FIGS. 14A through 14C show flow diverters 10 of the present
invention installed within different aneurism types: small neck
aneurism 12a shown in FIG. 14A, wide neck aneurism 12b shown in
FIG. 14B, and fusiform aneurism 12c shown in FIG. 14C) of in vitro
models with human whole blood.
[0106] Referring now to FIGS. 15A through 20, in addition to the
above in vitro studies with simulated blood, lab studies with whole
blood also demonstrated a much quicker occlusion of a
pseudo-aneurysm compared to a bare stent. Tests were performed on
the device 150 shown in FIG. 9 (having thin-film sheet detailed in
SEM images of FIGS. 6A, 6B and 10A-11B) in vivo, and showed the
cessation of flow into an aneurysm sac almost immediately upon
deployment (i.e. less than 5 minutes from first angiogram
shot).
[0107] In vivo tests were conducted on swine with a surgically
created aneurysm in the carotids. Both the left and right carotid
had a surgically created wide neck aneurysm (approximately 7 mm
neck in diameter). These aneurysms were occluded by deployment of
the both the 200 (300) micron (thin film 116 in FIGS. 6A and 6B)
and 400 (500) micron (thin film 120 in FIGS. 7A and 7B) size
thin-film NiTi flow diverters across the neck of the aneurysms.
Prior to deploying the thin-film flow diversion device onto the
aneurysm sac, the aneurysm was widely patent, and free from any
obstructions or clots as demonstrated by angiography (illustrated
in the image of 18A). The first swine study used only 200 (300)
micron size fenestrations of thin film 116 in FIGS. 6A and 6B with
super-hydrophylic surface treatment.
[0108] FIG. 18B illustrates an angiogram of the same vessel in the
image of FIG. 18A two minutes after deployment of the device of the
present invention using the 300 micron fenestrated film 116 in
FIGS. 6A and 6B. Total occlusion of aneurysm sac is achieved
immediately following deployment of the device (i.e. first
angiogram shot somewhere close to 2 minutes). Flow into the
aneurysm sac was completely undetectable by the angiography shown
by FIG. 18B. This test shows that the aneurysm had become
hemodynamically quiescent or occluded within 0-2 minutes of flow
diverter deployment. This phenomenon occurred in all aneurysms
tested using the 200 (300) micron fenestrated film 116 in FIGS. 6A
and 6B.
[0109] When this particular in vivo test was repeated on a separate
swine study using 400 (500) micron diameter holes of thin film 120
in FIGS. 7A and 7B, it took approximately 30 minutes to 1 hour for
flow to cease into the aneurysm sac. This result suggests an ideal
or critical sized fenestration dependent upon anatomical features,
such as flow velocity and vessel size, such that a designated
fenestration size (with surface treatment) immediately occludes the
sac due to the fast deposition of fibrin and other blood products
onto the thin-film scaffolding. More importantly, even though the
holes may not have been sized at the ideal or critical dimension,
flow into these aneurysms was decreased sufficiently enough to
produce quiescence of the aneurysm sac.
[0110] The flow diverter devices were harvested the same day they
were deployed. Using both optical microscopy and SEM evaluation
clear deposition of blood products on all the fenestrations was
noted, most notably a fibrin structure mesh formed that prevented
flow through the holes. FIGS. 15A and 15B show microscopic image
photographs of different views of fibrin deposition of the in vitro
fusiform 300 micron thin film 116 using whole blood after 30
minutes. FIG. 16 shows an SEM image of fibrin deposition of the
same in vitro fusiform model using whole blood after 30 minutes. As
shown in FIG. 16, the left of the dotted line is deposition created
from thin film 116. FIG. 17 shows a zoomed-in image of the left
side of the SEM image of FIG. 16.
[0111] FIG. 19 is a photograph of the harvested aneurysm sac of
FIGS. 18A and 18B approximately 2 hours after angiogram of FIG.
18B, showing total occlusion of aneurism, and completely contained
thrombii. FIG. 20 is an SEM image of the harvested aneurysm sac of
FIG. 19, showing complete fibrin deposition of the implant.
[0112] When evaluating the results of these studies, it is readily
apparent that after only a few minutes in the circulation system,
fibrin begins to deposit onto the thin film fenestrations of the
present invention flow diverters. The combination of the thin-film
meshwork and fibrin begin impeding flow very quickly. Therefore,
the flow reduction in a biological entity is likely attributed to
both the fenestration limiting flow (e.g. as seen in the simulated
blood experiments) but also from the rapid deposition of blood
products such as fibrin on the thin film. The in vivo results
described above demonstrate dramatic occlusion of even large
aneurysm sacs.
[0113] This rapid fibrin deposition, or clotting cascade, is
believed to be initiated by the unique structural configuration of
the thin-film flow diverters of the present invention, i.e. the
relative size of the fenestrations in the thin-film that begin to
approach the physical dimensions of the blood products. To another
extent, the surface treatment may also provide added fibrin
deposition or clotting cascade functionality. The flow environment
surrounding the thin-film is also a factor that influences the rate
at which the device binds to blood products (especially
fibrin).
[0114] The thin-film flow diverter of the present invention
produces a dramatic effect on the flow dynamics into anatomical
feature such as, for example, an aneurysm. This in turn activates
the clotting cascade only within the aneurysm. The thin-film
meshwork has also been shown both in vivo and in vitro to isolate
the parent artery from the large thrombus within the aneurysm.
Thus, the methods and devices of the present invention can not only
cause rapid thrombus formation within an aneurysm, but also protect
the native artery from embolization of this thrombus.
[0115] It is important to note that this clotting cascade does not
occur rapidly in large diameter holes such as stents. Coverings on
the order of 1 mm were tested, and did not result in fast
deposition of fibrin that was observed in the small-dimension
fenestrations of the thin films of the present invention. It is
also noteworthy that the devices of the present invention do not
produce thrombus formation within the parent artery. Long term in
vivo studies have shown these devices to be free of clot and
excessive neointimal hyperplasia in the parent arteries.
[0116] In conclusion, these studies found that ultra-thin high
porous material can dramatically reduce the flow within the sac and
could be used for any flow diverting vascular devices. This flow
reduction is due in part to the geometry chosen, the decrease in
pore size, and the increase in the relative surface area around the
perimeter of the hole to surface area ratio (i.e. this value
increases as hole size decreases even though surface coverage is
constant). This flow diversion may also be partially attributed to
the surface treatment that the film underwent prior to testing.
Because thin-film Nitinol flow diverters of the present invention
also allow for the creation of extremely flexible and low profile
neurovascular flow diversion devices, this work represents a major
breakthrough for this field that would have not been previously
considered possible by the community. The -film Nitinol flow
diverters of the present invention enable the creation of many
different forms of flow diversion devices that are non-thrombogenic
(reduction in surface area contacting blood), low profile, flexible
and that can divert flow without negatively impacting the specific
treatment proposed (e.g. for aneurysm flow diverter not occluding
parent or perforating vessels).
[0117] Thin-film flow diverters of the present invention allow for
the production of ultra-low profile neurovascular devices. Although
Nitinol was used as the preferable material in these studies, it is
contemplated that other materials may also be used for these
applications. Not only are these devices lower profile than the
current state of the art flow diversion device (Pipeline Stent,
EV3), but they are much more flexible, less thrombogenic, and have
significantly lower percent coverage of the aneurysm sac (i.e.
compare 10-20% to 30% for Pipeline). The present invention flow
diverters allow for use of the most minimal amounts of material
necessary for the treatment of small aneurysms. The flow diverter
of the present invention may be collapsed in a 3 Fr microdelivery
catheter, delivered through highly tortuous vascular structure, and
deployed with self-expanding mechanism to create intra-aneurismal
thrombosis in short time periods with minimal occlusion of
perforating vessels.
[0118] The device of the present invention also provides a
particular advantage in preventing thrombus from migrating from the
sac of a broad neck or fusiform aneurysm into the parent vessel
(e.g. prevents strokes). The device of the present invention
provides particular unexpected thrombotic effects with respect to
the aneurysm that have protective effects to the parent vessel.
Specifically, once the device of the present invention is covered
in native proteins, it is even more invisible to the parent vessel,
and less likely to induce clots in the parent vessel.
[0119] While the above advantages are directed to one particular
application, it is appreciated that the flow diverter of the
present invention can be used in a wide range of other vascular
applications.
[0120] In summary, the above description details a diversion device
that has minimal surface area, but produces dramatic changes in
flow patterns. Specifically for the brain aneurysm problem,
researchers have long believed based on available literature that
coverage areas must be greater than 30% to achieve occlusion. The
findings of the present invention have has shown that this is not
the case for appropriately fenestrated thin films. Thus, the
results of the present invention are unexpected in light of the
previous literature, which has taught away from using less that 30%
coverage to achieve occlusion.
[0121] It will be appreciated, therefore, that the invention can be
embodied in various ways, which include but are not limited to the
following.
[0122] 1. A flow diversion apparatus for diverting blood flow from
a treatment region, comprising: a thin-film sheet configured to be
positioned adjacent the treatment region; the thin-film sheet
comprising a plurality of fenestrations; wherein the fenestrations
are sized to generate a clotting cascade at the treatment
region.
[0123] 2. A flow diversion apparatus according to embodiment 1:
wherein the treatment region comprises an aneurism; and wherein the
clotting cascade is configured to occlude the aneurism.
[0124] 3. The flow diversion apparatus of embodiment 1, wherein the
fenestrations have a pore size of less than approximately 500
microns.
[0125] 4. The flow diversion apparatus of embodiment 3, wherein the
fenestrations have a pore size of less than approximately 300
microns.
[0126] 5. The flow diversion apparatus of embodiment 3, wherein the
fenestrations have a pore size between approximately 200 microns
and 400 microns.
[0127] 6. The flow diversion apparatus of embodiment 1, wherein the
thin-film sheet comprises a surface coverage of less than
approximately 30%.
[0128] 7. The flow diversion apparatus of embodiment 6, wherein the
thin-film sheet comprises a surface coverage of between
approximately 5% and 20%.
[0129] 8. The flow diversion apparatus of embodiment 1, wherein the
thin-film sheet comprises thin-film Nitinol having at least one
super-hydrophilic surface.
[0130] 9. The flow diversion apparatus of embodiment 8, wherein the
super-hydrophilic surface has a water contact angle of less than
approximately 5 degrees.
[0131] 10. The flow diversion apparatus of embodiment 8, wherein
the super-hydrophilic surface is configured to deter platelet
adhesion at a rate of less than 3 parts per mm.sup.2 when subjected
to platelet rich plasma for 3 or more hours.
[0132] 11. The flow diversion apparatus of embodiment 1, wherein
the fenestrations comprise at least one sharp edge.
[0133] 12. The flow diversion apparatus of embodiment 11, wherein
the fenestrations comprise diamond-shaped apertures.
[0134] 13. The flow diversion apparatus of embodiment 3, wherein
the fenestrations are fabricated using micro-machined thin-film
Nitinol.
[0135] 14. The flow diversion apparatus of embodiment 1, wherein
the fenestrations are fabricated using steps comprising: creating
trenches using photolithography and deep reactive ion etching
(DRIE); and depositing a Cu sacrificial layer and 500 nm SiO2
barrier layer by e-beam evaporation and PECVD.
[0136] 15. The flow diversion apparatus of embodiment 1, wherein
the fenestrations are configured to promote rapid binding of fibrin
to the thin-film sheet.
[0137] 16. The flow diversion apparatus of embodiment 1, further
comprising: a collapsible stent; wherein the thin-film sheet is
disposed over the stent.
[0138] 17. A vascular implant for occluding an aneurism,
comprising: a thin-film sheet configured to be positioned adjacent
the treatment region; the thin-film sheet comprising a plurality of
fenestrations; wherein the fenestrations are sized to generate a
clotting cascade at the aneurism.
[0139] 18. The vascular implant of embodiment 17, wherein the
fenestrations have a pore size between approximately 200 microns
and 400 microns.
[0140] 19. The vascular implant of embodiment 18, wherein the
thin-film sheet comprises a surface coverage of between
approximately 5% and 20%.
[0141] 20. A method of fabricating a thin-film sheet comprising an
array of fenestrations, the fenestrations having a pore size of
less than approximately 500 microns with a shape and size that is
substantially identical throughout the array, the method
comprising: creating trenches in a thin-film sheet of material
using photolithography and deep reactive ion etching (DRIE); and
depositing a Cu sacrificial layer and 500 nm SiO.sub.2 barrier
layer by e-beam evaporation and PECVD.
[0142] 21. The method of embodiment 20, wherein the thin film
comprises
[0143] Nitinol, the method further comprising: depositing Nitinol
by DC sputtering process onto the SiO2; removing the Cu and SiO2
layers; and crystallizing remaining film at 500.degree. C. for 120
minutes in a vacuum of less than 33 10-7 torr.
[0144] 22. The method of embodiment 20, wherein the fenestrations
have a pore size between approximately 200 microns and 400
microns.
[0145] 23. The method of embodiment 20, wherein the thin-film sheet
comprises a surface coverage of less than approximately 30%.
[0146] 24. The method of embodiment 20, wherein the thin-film sheet
comprises a surface coverage of between approximately 5% and
20%.
[0147] 25. The method of embodiment 20, wherein the fenestrations
comprise at least one sharp edge.
[0148] 26. The method of embodiment 25, wherein the fenestrations
comprise diamond-shaped apertures.
[0149] 27. The method of embodiment 25, wherein the thickness of
the thin-film sheet ranges between about 4 .mu.m and about 12
.mu.m.
[0150] 28. The method of embodiment 25, wherein the thickness of
the thin-film sheet ranges between about 6 .mu.m and about 8
.mu.m.
[0151] 29. The method of embodiment 25, wherein the thin-film sheet
is configured to elongate to over 400% of is original size without
substantial deformation.
[0152] 30. A method for diverting blood flow from a treatment
region, comprising: delivering a flow diverter to the treatment
region; and generating a clotting cascade at the treatment
region.
[0153] 31. The method of embodiment 30, wherein the flow diverter
comprises a thin-film sheet having an array of fenestrations have a
pore size between approximately 200 microns and 400 microns.
[0154] 32. The method of embodiment 31, wherein the thin-film sheet
comprises a surface coverage of less than approximately 30%.
[0155] 33. The method of embodiment 32, wherein the thin-film sheet
comprises a surface coverage of between approximately 5% and
20%.
[0156] 34. The method of embodiment 31, wherein the thickness of
the thin-film sheet ranges between about 6 .mu.m and about 8
.mu.m.
[0157] 35. The method of embodiment 31, wherein the fenestrations
are configured to promote rapid binding of fibrin to the thin-film
sheet.
[0158] 36. A method for occluding blood flow at an aneurism of a
vessel, comprising: delivering a vascular implant to the aneurism;
and generating a clotting cascade at the aneurism.
[0159] 37. The method of embodiment 36, wherein the vascular
implant comprises a thin-film sheet having an array of
fenestrations have a pore size between approximately 200 microns
and 400 microns.
[0160] 38. The method of embodiment 30, further comprising
preventing thrombus from migrating from the aneurism to the
vessel.
[0161] 39. The method of embodiment 38, wherein the aneurism
comprises a broad neck or fusiform aneurysm.
[0162] 40. The method of embodiment 37, wherein the thin-film sheet
comprises a surface coverage of between approximately 5% and
20%.
[0163] 41. The method of embodiment 37, wherein the thickness of
the thin-film sheet ranges between about 6 .mu.m and about 8
.mu.m.
[0164] 42. The method of embodiment 37: wherein the fenestrations
are configured to promote rapid binding of fibrin to the thin-film
sheet; and wherein said rapid binding of fibrin results in
substantial occlusion of flow into the aneurism within one hour of
delivering the flow diverter to the treatment region.
[0165] Although the description above contains many details, these
should not be construed as limiting the scope of the invention but
as merely providing illustrations of some of the presently
preferred embodiments of this invention. Therefore, the scope of
the present invention fully encompasses other embodiments which may
become obvious to those skilled in the art, and that the scope of
the present invention is accordingly to be limited by nothing other
than the appended claims, in which reference to an element in the
singular is not intended to mean "one and only one" unless
explicitly so stated, but rather "one or more." All structural,
chemical, and functional equivalents to the elements of the
above-described preferred embodiment that are known to those of
ordinary skill in the art are expressly incorporated herein by
reference and are intended to be encompassed by the present claims.
Moreover, it is not necessary for a device or method to address
each and every problem sought to be solved by the present
invention, for it to be encompassed by the present claims.
Furthermore, no element, component, or method step in the present
disclosure is intended to be dedicated to the public regardless of
whether the element, component, or method step is explicitly
recited in the claims. No claim element herein is to be construed
under the provisions of 35 U.S.C. 112, sixth paragraph, unless the
element is expressly recited using the phrase "means for."
* * * * *