U.S. patent application number 13/161343 was filed with the patent office on 2011-10-06 for stent coating apparatus using focused acoustic energy.
This patent application is currently assigned to Abbott Cardiovascular Systems Inc.. Invention is credited to Yung-Ming Chen, Lothar Kleiner, Jason Van Sciver.
Application Number | 20110239939 13/161343 |
Document ID | / |
Family ID | 44245495 |
Filed Date | 2011-10-06 |
United States Patent
Application |
20110239939 |
Kind Code |
A1 |
Van Sciver; Jason ; et
al. |
October 6, 2011 |
STENT COATING APPARATUS USING FOCUSED ACOUSTIC ENERGY
Abstract
An apparatus for coating a stent includes an optical feedback
system used to align a transducer with a stent strut. Once
alignment is achieved, the transducer causes a coating to be
ejected onto the stent strut and the transducer is moved along the
stent strut to coat the stent strut.
Inventors: |
Van Sciver; Jason; (Los
Gatos, CA) ; Chen; Yung-Ming; (Cupertino, CA)
; Kleiner; Lothar; (Los Altos, CA) |
Assignee: |
Abbott Cardiovascular Systems
Inc.
Santa Clara
CA
|
Family ID: |
44245495 |
Appl. No.: |
13/161343 |
Filed: |
June 15, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11305662 |
Dec 16, 2005 |
7976891 |
|
|
13161343 |
|
|
|
|
Current U.S.
Class: |
118/708 |
Current CPC
Class: |
B05D 1/002 20130101 |
Class at
Publication: |
118/708 |
International
Class: |
B05C 11/00 20060101
B05C011/00 |
Claims
1. A stent coating apparatus, comprising: a transducer capable of
ejecting droplets of a coating substance from a reservoir; and an
optical feedback system that aligns the transducer with a stent
strut such that the coating substance is delivered to a stent
strut.
2. The apparatus of claim 1, wherein the optical feedback system
causes the movement of the transducer relative to the stent strut
while the coating is being delivered.
3. The apparatus of claim 1, wherein the optical feedback system
aligns the transducer with the stent strut via rotation and
translation of the stent.
4. The apparatus of claim 1, wherein the optical feedback system
aligns the transducer with the stent strut via rotation of the
stent and translation of the transducer.
5. The apparatus of claim 1, wherein the optical feedback system
verifies the coating on the stent strut and causes recoating of the
stent strut if the coating is determined to be inadequate.
6. The apparatus of claim 1, wherein energy from the transducer is
focused on a fluid meniscus of the coating substance.
7. The apparatus of claim 6, wherein the optical feedback system is
positioned to view the fluid meniscus and further capable of moving
the transducer relative to the fluid meniscus to maintain focus on
the fluid meniscus.
8. The apparatus of claim 1, wherein energy from the transducer is
focused at the interface of the coating substance and a second
coating substance in the reservoir.
9. The apparatus of claim 1, wherein the transducer is located
within an ejector holding the coating substance.
10. The apparatus of claim 1, wherein the transducer is external to
a reservoir housing holding the reservoir.
11. The apparatus of claim 1, wherein the transducer is external to
a reservoir housing holding a plurality of coating substances in
individual reservoir compartments.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional of application Ser. No.
11/305,662, filed Dec. 16, 2005, which is incorporated herein by
reference.
TECHNICAL FIELD
[0002] This invention relates generally to stent coating
apparatuses, and more particularly, but not exclusively, provides
an assembly and method for coating of an abluminal stent surface by
dispensing coating using acoustic energy.
BACKGROUND
[0003] Blood vessel occlusions are commonly treated by mechanically
enhancing blood flow in the affected vessels, such as by employing
a stent. Stents act as scaffoldings, functioning to physically hold
open and, if desired, to expand the wall of affected vessels.
Typically stents are capable of being compressed, so that they can
be inserted through small lumens via catheters, and then expanded
to a larger diameter once they are at the desired location.
Examples in the patent literature disclosing stents include U.S.
Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued
to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.
[0004] FIG. 1 illustrates a conventional stent 10 formed from a
plurality of struts 12. The plurality of struts 12 are radially
expandable and interconnected by connecting elements 14 that are
disposed between adjacent struts 12, leaving lateral openings or
gaps 16 between adjacent struts 12. The struts 12 and the
connecting elements 14 define a tubular stent body having an outer,
tissue-contacting surface and an inner surface.
[0005] Stents are being modified to provide drug delivery
capabilities. A polymeric carrier, impregnated with a drug or
therapeutic substance is coated on a stent. The conventional method
of coating is by, for example, applying a composition including a
solvent, a polymer dissolved in the solvent, and a therapeutic
substance dispersed in the blend to the stent by immersing the
stent in the composition or by spraying the composition onto the
stent. The solvent is allowed to evaporate, leaving on the stent
strut surfaces a coating of the polymer and the therapeutic
substance impregnated in the polymer. The dipping or spraying of
the composition onto the stent can result in a complete coverage of
all stent surfaces, i.e., both luminal (inner) and abluminal
(outer) surfaces, with a coating. However, having a coating on the
luminal surface of the stent can have a detrimental impact on the
stent's deliverability as well as the coating's mechanical
integrity. Moreover, from a therapeutic standpoint, the therapeutic
agents on an inner surface of the stent get washed away by the
blood flow and typically can provide for an insignificant
therapeutic effect. In contrast, the agents on the outer surfaces
of the stent are in contact with the lumen, and provide for the
delivery of the agent directly to the tissues. Polymers of a stent
coating also elicit a response from the body. Reducing the amount
to foreign material can only be beneficial.
[0006] Briefly, an inflatable balloon of a catheter assembly is
inserted into a hollow bore of a coated stent. The stent is
securely mounted on the balloon by a crimping process. The balloon
is inflated to implant the stent, deflated, and then withdrawn out
from the bore of the stent. A polymeric coating on the inner
surface of the stent can increase the coefficient of friction
between the stent and the balloon of a catheter assembly on which
the stent is crimped for delivery. Additionally, some polymers have
a "sticky" or "tacky" consistency. If the polymeric material either
increases the coefficient of friction or adherers to the catheter
balloon, the effective release of the stent from the balloon after
deflation can be compromised. If the stent coating adheres to the
balloon, the coating, or parts thereof, can be pulled off the stent
during the process of deflation and withdrawal of the balloon
following the placement of the stent. Adhesive, polymeric stent
coatings can also experience extensive balloon sheer damage
post-deployment, which could result in a thrombogenic stent surface
and possible embolic debris. The stent coating can stretch when the
balloon is expanded and may delaminate as a result of such shear
stress.
[0007] Another shortcoming of the spray coating and immersion
methods is that these methods tend to form defects on stents, such
as webbing between adjacent stent struts 12 and connecting elements
14 and the pooling or clumping of coating on the struts 12 and/or
connecting elements 14. In addition, spray coating can cause
coating defects at the interface between a stent mandrel and the
stent 10 as spray coating will coat both the stent 10 and the stent
mandrel at this interface, possibly forming a clump. During removal
of the stent 10 from the stent mandrel, this clump may detach from
the stent 10, thereby leaving an uncoated surface on the stent 10.
Alternatively, the clump may remain on the stent 10, thereby
yielding a stent 10 with excessive coating.
[0008] Another shortcoming of the spray coating method is that a
nozzle in a spray coating apparatus can get clogged with
particulate when some of the coating substance solidifies. This
clogging can deflect or block the spray, thereby yielding an
unsatisfactory coating on the stent 10. The need to unclog a nozzle
can cause long periods of downtime for a spray coating apparatus,
thereby lowering production rates of stents.
[0009] Accordingly, a new apparatus and method are needed to enable
selective coating of stent surfaces while minimizing the formation
of defects and coating apparatus downtime.
SUMMARY OF THE INVENTION
[0010] Briefly and in general terms, the present invention is
directed to a stent coating apparatus. In aspects of the present
invention, an apparatus comprises a transducer capable of ejecting
droplets of a coating substance from a reservoir, and an optical
feedback system that aligns the transducer with a stent strut such
that the coating substance is delivered to a stent strut.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Non-limiting and non-exhaustive embodiments of the present
invention are described with reference to the following figures,
wherein like reference numerals refer to like parts throughout the
various views unless otherwise specified.
[0012] FIG. 1 is a diagram illustrating a conventional stent;
[0013] FIG. 2 is a block diagram illustrating a stent coating
apparatus according to an embodiment of the invention;
[0014] FIG. 3 is a block diagram illustrating a stent coating
apparatus according to another embodiment of the invention;
[0015] FIG. 4A and FIG. 4B (collectively, FIG. 4) are diagrams
illustrating cross sections of an ejector according to an
embodiment of the invention;
[0016] FIG. 5 is a block diagram illustrating a stent coating
apparatus according to another embodiment of the invention;
[0017] FIG. 6 is a is a diagram illustrating a cross section of an
ejector according to another embodiment of the invention;
[0018] FIG. 7 is a is a diagram illustrating a cross section of an
ejector according to another embodiment of the invention; and
[0019] FIG. 8 is a flowchart illustrating a method of coating an
abluminal stent surface.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0020] The following description is provided to enable any person
having ordinary skill in the art to make and use the invention, and
is provided in the context of a particular application and its
requirements. Various modifications to the embodiments will be
readily apparent to those skilled in the art, and the generic
principles defined herein may be applied to other embodiments and
applications without departing from the spirit and scope of the
invention. Thus, the present invention is not intended to be
limited to the embodiments shown, but is to be accorded the widest
scope consistent with the principles, features and teachings
disclosed herein.
[0021] FIG. 2 is a block diagram illustrating a stent coating
apparatus 200 according to an embodiment of the invention. The
apparatus 200, including a stent mandrel fixture 20 for supporting
the stent 10, is illustrated to include a support member 22, a
mandrel 24, and an optional lock member 26 (e.g., if the stent 10
can be supported by the mandrel 24 itself). The support member 22
can connect to a motor 30A so as to provide rotational motion about
the longitudinal axis of the stent 10, as depicted by arrow 32,
during a coating process. Another motor 30B can also be provided
for moving the support member 22 in a linear direction, back and
forth, along a rail 34.
[0022] The support member 22 includes a coning end portion 36,
tapering inwardly. In accordance with one embodiment of the
invention, the mandrel 24 can be permanently affixed to coning end
portion 36. Alternatively, the support member 22 can include a bore
38 for receiving a first end of the mandrel 24. The first end of
mandrel 24 can be threaded to screw into the bore 38 or,
alternatively, can be retained within the bore 38 by a friction
fit. The bore 38 should be deep enough so as to allow the mandrel
24 to securely mate with the support member 22. The depth of the
bore 38 can also be over-extended so as to allow a significant
length of the mandrel 24 to penetrate or screw into the bore 38.
The bore 38 can also extend completely through the support member
22. This would allow the length of the mandrel 24 to be adjusted to
accommodate stents of various sizes. The mandrel 24 also includes a
plurality of ridges 25 that add rigidity and support to the stent
10 during the coating process. The ridges 25 have a diameter of
slightly less than the inner diameter of stent 10. While three
ridges 25 are shown, it will be appreciated by one of ordinary
skill in the art that additional or fewer ridges may be present and
they may be evenly or unevenly spaced.
[0023] The lock member 26 includes a coning end portion 42 tapering
inwardly. A second end of the mandrel 24 can be permanently affixed
to the lock member 26 if the first end is disengagable from the
support member 22. Alternatively, in accordance with another
embodiment, the mandrel 24 can have a threaded second end for
screwing into a bore 46 of the lock member 26. The bore 46 can be
of any suitable depth that would allow the lock member 26 to be
incrementally moved closer to the support member 22. The bore 46
can also extend completely through the lock member 26. Accordingly,
the stents 10 of any length can be securely pinched between the
support and the lock members 22 and 26. In accordance with yet
another embodiment, a non-threaded second end and the bore 46
combination is employed such that the second end can be
press-fitted or friction-fitted within the bore 46 to prevent
movement of the stent 10 on the stent mandrel fixture 20.
[0024] Positioned a distance from the stent 10 (e.g., above the
stent 10) is a reservoir 210 holding a coating substance to be
applied to the stent 10. The reservoir 210 is in fluid
communication with an ejector 220 having an aperture 230. The
ejector 220 is also positioned a distance from the stent 10 (e.g.,
above, below and/or at an angle to the stent 10). Disposed within
the ejector 220 is a transducer 410 (FIG. 4) that converts
electrical energy into vibrational energy in the form of sound or
ultrasound. The sound or ultrasound (collectively referred to as
acoustic energy herein) ejects (or dispenses) drops of the coating
substance from the aperture 230 onto the stent 10. In an embodiment
of the invention, each acoustic pulse from the transducer 410
dispenses a single drop from the aperture 230.
[0025] The reservoir 210 dispenses the coating substance to the
ejector 220, which ejects it through the aperture 230, which will
be discussed in further detail in conjunction with FIG. 4 below.
The reservoir 210 can dispense the coating substance using gravity
and/or forced pressure (e.g., a pump) to the ejector 220. The
aperture 230 has a small opening of 50 .mu.m to 250 .mu.m and
therefore the coating substance will not exit the aperture 230 due
to surface tension and/or gravity unless the transducer 410 is
activated. In an embodiment of the invention, if the ejector 220 is
positioned underneath the stent 10 with the aperture 230 pointing
upwards, the ejector 220 can still be in the orientation shown in
FIG. 4 and gravity can be used to form a negative or positive
meniscus by placing the reservoir at a height above, even, or below
the exit aperture 230. Further, a low surface energy coating, such
as TEFLON, can coat the aperture 230 to eliminate coating exiting
the aperture except when desired. Accordingly, by using the
transducer 410 during the application of the coating substance, the
rate of coating dispensed can be adjusted so that certain sections
of the stent 10 receive more coating than others. If the coating
material is applied in an intermittent fashion, coating adjustments
can be made during the stoppage of coating application. Further,
the coating can be stopped while the ejector 220 is being
repositioned relative to the stent 10.
[0026] The ejector 220 is aligned with a stent strut 12 and coats
each individual stent strut 12. As will be discussed further below,
coating flows into the ejector 220 and is ejected from the aperture
230 by the transducer 410 onto the stent strut 12, thereby limiting
the coating to just the outer surface stent strut 12 and not other
surfaces (e.g., the luminal surface) as in spaying and immersion
techniques. In one embodiment, the sidewalls of the stent struts 12
between the outer and inner surfaces can be partially coated.
Partial coating of sidewalls can be incidental, such that some
coating can flow from the outer surface onto the sidewalls, or
intentional.
[0027] Coupled to the ejector 220 can be a first imaging device 250
that images the stent 10 before and/or after the coating substance
has been applied to a portion of the stent 10. The first imaging
device 250, along with a second imaging device 260 located a
distance from the stent 10, are both communicatively coupled to an
optical feedback system 270 via wired or wireless techniques. The
reservoir 210 may also be communicatively coupled to the optical
feedback system 270 via wired or wireless techniques. Based on the
imagery provided by the imaging devices 250 and 260, the optical
feedback system 270 controls movement of stent 10 via the motors
30A and 30B to keep the aperture 230 aligned with the stent struts
12 and recoat the stent struts 12 if improperly (or inadequately)
coated.
[0028] In an embodiment of the invention, the optical feedback
system 270 includes a network of components, at least one of which
performs movement while at least one other component determines the
movement to be made. In an embodiment of the invention, the optical
feedback system 270 can use other techniques besides optics to
image a stent, such as radar or electron scanning
[0029] During operation of the stent coating apparatus 200, the
optical feedback system 270 causes the imaging device 260 to image
the full surface of the stent 10 as the feedback system 270 causes
the motor 30A to rotate the stent 10. After the initial imaging,
the optical feedback system 270, using the imaging device 260,
aligns the aperture 230 with a stent strut 12 by causing the motors
30A and 30B to rotate and translate the stent 10 until alignment is
achieved. The optical feedback system 270 then causes the
transducer 410 (FIG. 4) to dispense the coating substance through
the aperture 230 by emitting acoustic energy towards coating
substance located in the aperture 230. As the coating substance is
dispensed, the optical feedback system 270 causes the motors 30A
and 30B to rotate and translate the stent 10 in relation to the
aperture 230 so as to position uncoated sections of the stent strut
12 along the aperture 230, thereby causing the entire abluminal
surface of the strut 12 to be coated.
[0030] After a portion of the stent strut 12 has been coated, the
optical feedback system 270 causes the transducer 410 to cease
dispensing the coating substance and causes the imaging device 250
to image the stent strut 12 to determine if the strut 12 has been
adequately coated. This determination can be made by measuring the
difference in color and/or reflectivity of the stent strut 12
before and after the coating process. If the strut 12 has been
adequately coated, then the optical feedback system 270 causes the
motors 30A and 30B to rotate and translate the stent 10 so that the
aperture 230 is aligned with an uncoated stent 10 section and the
above process is then repeated. If the stent strut 12 is not coated
adequately, then the optical feedback system 270 causes the motors
30A and 30B to rotate and translate the stent 10 and the transducer
410 to dispense the coating substance to recoat the stent strut 12.
In another embodiment of the invention, the optical feedback system
270 can cause checking and recoating of the stent 10 after the
entire stent 10 goes through a first coating pass.
[0031] In an embodiment of the invention, the imaging devices 250
and 260 include charge coupled devices (CCDs) or complementary
metal oxide semiconductor (CMOS) devices. In an embodiment of the
invention, the imaging devices 250 and 260 are combined into a
single imaging device. Further, it will be appreciated by one of
ordinary skill in the art that placement of the imaging devices 250
and 260 can vary as long as they have an acceptable view of the
stent 10. In addition, one of ordinary skill in the art will
realize that the stent mandrel fixture 20 can take any form or
shape as long as it is capable of securely holding the stent 10 in
place.
[0032] Accordingly, embodiments of the invention enable the fine
coating of specific surfaces of the stent 10, thereby avoiding
coating defects that can occur with spray coating and immersion
coating methods and limiting the coating to only the abluminal
surface and/or sidewalls of the stent 10. In another embodiment,
the coating can be limited to depots or patterns as described in
U.S. Pat. No. 6,395,326, which is incorporated herein by reference.
Application of the coating in the gaps 16 between the stent struts
12 can be partially, or preferable completely, avoided.
[0033] After the brush coating of the stent 10 abluminal surface,
the stent 10 can then have the inner surface coated via
electrospraying or spray coating. Without masking the outer surface
of the stent 10, both electrospraying and spray coating may yield
some composition onto the outer surface and sidewalls of the stent
10. However, the inner surface would be substantially solely coated
with a single composition different from the composition used to
coat the outer surface of the stent 10. Accordingly, it will be
appreciated by one of ordinary skill in the art that this
embodiment enables the coating of the inner surface and the outer
surface of the stent 10 with different compositions. For example,
the inner surface could be coated with a composition having a
bio-beneficial therapeutic substance for delivery downstream of the
stent 10 (e.g., an anticoagulant, such as heparin, to reduce
platelet aggregation, clotting and thrombus formation) while the
outer surface of the stent 10 could be coating with a composition
having a therapeutic substance for local delivery to a blood vessel
wall (e.g., an anti-inflammatory drug to treat vessel wall
inflammation or a drug for the treatment of restenosis).
[0034] The components of the coating substance or composition can
include a solvent or a solvent system comprising multiple solvents,
a polymer or a combination of polymers, a therapeutic substance or
a drug or a combination of drugs. In some embodiments, the coating
substance can be exclusively a polymer or a combination of polymers
(e.g., for application of a primer layer or topcoat layer). In some
embodiments, the coating substance can be a drug that is polymer
free. Polymers can be biostable, bioabsorbable, biodegradable, or
bioerodable. Biostable refers to polymers that are not
biodegradable. The terms biodegradable, bioabsorbable, and
bioerodable are used interchangeably and refer to polymers that are
capable of being completely degraded and/or eroded when exposed to
bodily fluids such as blood and can be gradually resorbed,
absorbed, and/or eliminated by the body. The processes of breaking
down and eventual absorption and elimination of the polymer can be
caused by, for example, hydrolysis, metabolic processes, bulk or
surface erosion, and the like.
[0035] Representative examples of polymers that may be used
include, but are not limited to, poly(N-acetylglucosamine)
(Chitin), Chitoson, poly(hydroxyvalerate),
poly(lactide-co-glycolide), poly(hydroxybutyrate),
poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride,
poly(glycolic acid), poly(glycolide), poly(L-lactic acid),
poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide),
poly(D-lactic acid), poly(D-lactide), poly(caprolactone),
poly(trimethylene carbonate), polyester amide, poly(glycolic
acid-co-trimethylene carbonate), co-poly(ether-esters) (e.g.
PEO/PLA), polyphosphazenes, biomolecules (such as fibrin,
fibrinogen, cellulose, starch, collagen and hyaluronic acid),
polyurethanes, silicones, polyesters, polyolefins, polyisobutylene
and ethylene-alphaolefin copolymers, acrylic polymers and
copolymers other than polyacrylates, vinyl halide polymers and
copolymers (such as polyvinyl chloride), polyvinyl ethers (such as
polyvinyl methyl ether), polyvinylidene halides (such as
polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones,
polyvinyl aromatics (such as polystyrene), polyvinyl esters (such
as polyvinyl acetate), acrylonitrile-styrene copolymers, ABS
resins, polyamides (such as Nylon 66 and polycaprolactam),
polycarbonates, polyoxymethylenes, polyimides, polyethers,
polyurethanes, rayon, rayon-triacetate, cellulose, cellulose
acetate, cellulose butyrate, cellulose acetate butyrate,
cellophane, cellulose nitrate, cellulose propionate, cellulose
ethers, and carboxymethyl cellulose. Representative examples of
polymers that may be especially well suited for use include
ethylene vinyl alcohol copolymer (commonly known by the generic
name EVOH or by the trade name EVAL), poly(butyl methacrylate),
poly(vinylidene fluoride-co-hexafluororpropene) (e.g., SOLEF 21508,
available from Solvay Solexis PVDF, Thorofare, N.J.),
polyvinylidene fluoride (otherwise known as KYNAR, available from
ATOFINA Chemicals, Philadelphia, Pa.), ethylene-vinyl acetate
copolymers, and polyethylene glycol.
[0036] "Solvent" is defined as a liquid substance or composition
that is compatible with the polymer and/or drug and is capable of
dissolving the polymer and/or drug at the concentration desired in
the composition. Examples of solvents include, but are not limited
to, dimethylsulfoxide, chloroform, acetone, water (buffered
saline), xylene, methanol, ethanol, 1-propanol, tetrahydrofuran,
1-butanone, dimethylformamide, dimethylacetamide, cyclohexanone,
ethyl acetate, methylethylketone, propylene glycol monomethylether,
isopropanol, isopropanol admixed with water, N-methyl
pyrrolidinone, toluene, and mixtures and combinations thereof.
[0037] The therapeutic substance or drug can include any substance
capable of exerting a therapeutic or prophylactic effect. Examples
of active agents include antiproliferative substances such as
actinomycin D, or derivatives and analogs thereof (manufactured by
Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233;
or COSMEGEN available from Merck). Synonyms of actinomycin D
include dactinomycin, actinomycin IV, actinomycin I.sub.1,
actinomycin X.sub.1, and actinomycin C.sub.1. The bioactive agent
can also fall under the genus of antineoplastic, anti-inflammatory,
antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic,
antibiotic, antiallergic and antioxidant substances. Examples of
such antineoplastics and/or antimitotics include paclitaxel, (e.g.,
TAXOL.RTM. by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel
(e.g., Taxotere.RTM., from Aventis S.A., Frankfurt, Germany),
methotrexate, azathioprine, vincristine, vinblastine, fluorouracil,
doxorubicin hydrochloride (e.g., Adriamycin.RTM. from Pharmacia
& Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin.RTM.
from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such
antiplatelets, anticoagulants, antifibrin, and antithrombins
include aspirin, sodium heparin, low molecular weight heparins,
heparinoids, hirudin, argatroban, forskolin, vapiprost,
prostacyclin and prostacyclin analogues, dextran,
D-phe-pro-arg-chloromethylketone (synthetic antithrombin),
dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor
antagonist antibody, recombinant hirudin, and thrombin inhibitors
such as Angiomax a (Biogen, Inc., Cambridge, Mass.). Examples of
such cytostatic or antiproliferative agents include angiopeptin,
angiotensin converting enzyme inhibitors such as captopril (e.g.,
Capoten.RTM. and Capozide.RTM. from Bristol-Myers Squibb Co.,
Stamford, Conn.), cilazapril or lisinopril (e.g., Prinivil.RTM. and
Prinzide.RTM. from Merck & Co., Inc., Whitehouse Station,
N.J.), calcium channel blockers (such as nifedipine), colchicine,
proteins, peptides, fibroblast growth factor (FGF) antagonists,
fish oil (omega 3-fatty acid), histamine antagonists, lovastatin
(an inhibitor of HMG-CoA reductase, a cholesterol lowering drug,
brand name Mevacor.RTM. from Merck & Co., Inc., Whitehouse
Station, N.J.), monoclonal antibodies (such as those specific for
Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside,
phosphodiesterase inhibitors, prostaglandin inhibitors, suramin,
serotonin blockers, steroids, thioprotease inhibitors,
triazolopyrimidine (a PDGF antagonist), and nitric oxide. An
example of an antiallergic agent is permirolast potassium. Other
therapeutic substances or agents which may be appropriate agents
include cisplatin, insulin sensitizers, receptor tyrosine kinase
inhibitors, carboplatin, alpha-interferon, genetically engineered
epithelial cells, steroidal anti-inflammatory agents, non-steroidal
anti-inflammatory agents, antivirals, anticancer drugs,
anticoagulant agents, free radical scavengers, estradiol,
antibiotics, nitric oxide donors, super oxide dismutases, super
oxide dismutases mimics,
4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO),
tacrolimus, dexamethasone, ABT-578, clobetasol, cytostatic agents,
prodrugs thereof, co-drugs thereof, and a combination thereof.
Other therapeutic substances or agents may include rapamycin and
structural derivatives or functional analogs thereof, such as
40-O-(2-hydroxy) ethyl-rapamycin (everolimus),
40-O-(3-hydroxy)propyl-rapamycin,
40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and
40-O-tetrazole-rapamycin.
[0038] FIG. 3 is a block diagram illustrating a stent coating
apparatus 300 according to another embodiment of the invention. The
stent coating apparatus 300 is similar to the stent coating
apparatus 200. However, the ejector 220 is capable of translational
movement along a guide rail 310. Accordingly, the alignment of the
aperture 230 with a stent strut 12 is accomplished by the optical
feedback system 270 causing the engine 30A to rotate the stent 10
in combination with causing the brush assembly 230 to move along
the guard rail 310. The guard rail 310 should be at least about as
long as the stent 10 to enable the ejector 220 full mobility over
the length of the stent 10. In some embodiments, the ejector 220 is
capable of translational movement along the guide rail 310 in
combination contemporaneously or in turn with rotation and
translation of the stent 10.
[0039] In another embodiment of the invention, the ejector 220 is
coupled to a painting robot, such as one have six axes (three for
the base motions and three for applicator orientation) that
incorporates machine vision and is electrically driven.
Accordingly, the ejector 220 can fully rotate around and translate
along a stent 10 in a stationary position. Alternatively, both the
ejector 220 and the stent 10 can rotate and/or translate
contemporaneously or in turn. For example, the ejector 220 can move
for alignment with a strut of the stent 10 while the stent 10 can
move during coating after alignment, vice versa, or a combination
of both.
[0040] In any of the above-mentioned embodiments, the coating
process can be continuous, i.e., the ejector 220 can move along and
coat the entire stent 10 without stopping, or move intermittently,
i.e., coating a first section of the stent 10, stopping, and then
aligning with a second section of the stent 10, and coating that
second section. The second section may be adjacent to the first
section or located a distance from the first section.
[0041] FIG. 4A is a diagram illustrating cross section of the
ejector 220 having the aperture 230 and the transducer 410
according to an embodiment of the invention. The ejector 220
includes a transducer system 400 including the transducer 410,
which can be piezoelectric, a cavity 420, and an acoustic lens 430.
The transducer 410 is positioned a distance from the aperture 230.
The transducer 410 converts electrical energy into unidirectional
acoustic energy, which travels through the cavity 420 and is
focused on the aperture 230 where the fluid meniscus is located by
the acoustic lens 430. The acoustic lens 430 can be concave in
shape. The focused energy causes an increase in pressure to cause
droplets to drop off. The transducer 410 can include (or be coupled
to) drive electronics, such as power supplies, RF amplifier, RF
switches, and pulsers; an acoustic lens assembly; a fluid reservoir
and level control hardware; and/or an imaging system for online
monitoring for drop size and velocity. As the reservoir constantly
feeds the coating substance to the ejector 220 during coating
applications, the meniscus stays level, thereby preventing the need
for the transducer 410 to be refocused. While the ejector 220 is
shown with the aperture 230 facing downwards, it will be
appreciated by one of ordinary skill in the art that the ejector
220 can employed with the aperture 230 facing upwards or otherwise
positioned with respect to the stent 10.
[0042] The acoustic energy causes the ejection of drops of the
coating substance due to an acoustic pressure transient at the
meniscus and prevents clogging of the aperture 230 since the
ejected drops do not come in contact with the aperture 230 during
ejection. The acoustic energy can have a frequency of about 500 Hz
to about 5000 Hz. The firing rate can range from about 1 to 3000
Hz. In an embodiment of the invention, the aperture 230 has a
diameter of less than about 20 microns, leading to drops with a
maximum diameter about 20 microns. In another embodiment of the
invention, the aperture 230 has a diameter of about 10 microns to
about 50 microns, yielding similar-sized drops. Drop volume can
range from about 5 picoliters to about 30 picoliters. Drop diameter
decreases exponentially as frequency increases. Pulse widths can
vary from about 10 .mu.sec to about 60 .mu.sec.
[0043] FIG. 4B is a diagram illustrating another embodiment of the
transducer system 400. The transducer system 400 transmits acoustic
energy to the meniscus of a coating substance (shown in black) at
an aperture 450 of a plate 440.
[0044] FIG. 5 is a block diagram illustrating a stent coating
apparatus 500 according to another embodiment of the invention. The
stent coating apparatus 500 is similar to the stent coating
apparatus 200. However, in place of the reservoir 210 is a
reservoir housing 510 having a plurality of reservoirs 605 (FIG. 6)
(e.g., wells) located beneath the stent 10. The reservoirs 605 each
hold a coating substance. A transducer 520 is located beneath the
reservoir housing 510 and is not in contact with the coating
substance. The transducer 520 is substantially similar to the
transducer 410 and transmits acoustic energy at one of the
plurality of reservoirs 605 focused on the surface of the coating
substance, as will be discussed in further detail below.
[0045] FIG. 6 is a diagram illustrating a cross section an ejector
comprising the reservoir housing 510 and the transducer 520. The
transducer 520 outputs acoustic energy at a reservoir 605 focused
at the surface of the coating substance 600 therein. Each pulse
ejects a known amount of the substance 600 in a droplet 620 from
the reservoir onto the stent 10, thereby decreasing the substance
600 level in the reservoir 605. Accordingly, after each pulse of
acoustic energy, the transducer 520 can be refocused to the new
level in the reservoir 605. In an alternative embodiment, the
reservoirs can be constantly refilled, thereby keeping the
substance 600 level the same throughout the stent 10 coating
process. In an embodiment of the invention, the reservoirs 605 can
each hold different coating substances, e.g., a first reservoir can
hold substance 600 while a second reservoir can hold substance 610.
The transducer 520 can then cause the ejection of different coating
substances onto the stent 10 during a single application process.
Further, as there is no contact between the transducer 520 and
reservoirs 605, there is no chance of cross contamination between
reservoirs 605 or clogging of any ejectors.
[0046] In an embodiment of the invention, the apparatus 500 further
includes a third imaging device 630 positioned to image the fluid
meniscus in the reservoirs 605. The imaging device 630 is
communicatively coupled to the optical feedback system 270, which
is further capable of determining the height of the fluid meniscus
in the reservoirs 605 and adjusting the transducer 520 accordingly
(e.g., moving the transducer 520 vertically) to maintain focus on
the fluid meniscus as the fluid meniscus moves to ensure optimal
drop size and velocity.
[0047] In the embodiment shown in FIG. 7, one or more of the
reservoirs 605 may contain two different coating substances, e.g.,
the coating substance 610 and a coating substance 710. The
transducer 520 ejects a combined drop 720 from the reservoir by
focusing a pulse of acoustic energy at the interface between the
two substances. Accordingly, the stent 10 can be coated
simultaneously with two different coating substances.
[0048] FIG. 8 is a flowchart illustrating a method 800 of coating
an abluminal stent surface. In an embodiment of the invention, the
system 200, 300 or 500 can implement the method 800. First, an
image of the stent 10 is captured (810) as the stent 10 is rotated.
Based on the captured image, an ejector is aligned (820) with a
stent strut 12 of the stent 10 via rotation and/or translation of
the stent 10 and/or translation/rotation of the transducer. A
coating is then dispensed (830) onto the stent via acoustic
ejection of a coating substance. As the coating is being dispensed
(830), the ejector and/or stent are moved (840) relative to each
other so as to coat at least a portion of the stent strut 12. The
coating process could involve vision guided motion such that the
stent is coated as the vision system guides the stent under the
nozzle or the nozzle over the stent. Alternatively, the vision
system could image the entire stent first then cause the stent to
move under the nozzle or the nozzle over the stent for the duration
of the coating process.
[0049] The dispensing is then stopped (845), and an image of at
least a portion of the stent that was just coated in captured
(850). Using the captured image, the coating is verified (860)
based on color change, reflectivity change, and/or other
parameters. If (870) the coating is not verified (e.g., the stent
strut 12 was not fully coated), then the strut 12 is recoated (890)
by realigning the transducer with the strut 12, dispensing the
coating, and moving the ejector relative to the strut. Capturing
(850) an image and verifying (860) are then repeated.
[0050] If (870) the coating is verified and if (880) the stent has
been completely coated, then the method 800 ends. Otherwise, the
method 800 is repeated with a different stent strut starting with
the aligned (820).
[0051] In an embodiment of the invention, the luminal surface of
the stent 10 can then be coated with a different coating using
electroplating or other technique. Accordingly, the abluminal
surface and the luminal surface can be coated with different
coatings. Further, the entire stent 10 can be coated (830) before
verification (860) of the entire stent 10 or portions thereof.
[0052] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from this invention in its broader aspects. For example,
multiple reservoirs and transducers can be used simultaneously to
speed up the coating of a stent. Further, the multiple reservoirs
can contain different coating substances such that different
coating substances can be applied to different regions of a stent
substantially simultaneously. Therefore, the appended claims are to
encompass within their scope all such changes and modifications as
fall within the true spirit and scope of this invention.
* * * * *