High strength vacuum deposited nitionol alloy films, medical thin film graft materials and method of making same

Description of equivalent WO 2004028340 A2

Title

[0001] High Strength Vacuum Deposited Nitinol Alloy Films, Medical Thin Film

Graft Materials and Method of Making Same.

Background of the Invention

[0002] The present invention relates generally to high-strength shape memory and superelastic alloys and vacuum deposited metallic materials. More specifically, the present invention relates to nickel-based and titanium-based alloys fabricated by vacuum deposition technologies and which exhibit shape memory effect (SME) and/or superelastic behavior. The present invention also relates to the field of implantable medical devices intended to maintain patency of anatomical passageways, such as those found in the cardiovascular, lymphatic, endocrine, renal, gastrointestinal and/or reproductive systems of mammals. More particularly, the present invention relates to grafts that are designed for endoluminal delivery using a delivery catheter and minimally invasive surgical techniques. The present invention generally comprises grafts or graft assemblies, such as stent-grafts and covered stents, that are fabricated entirely of biocompatible metals or of biocompatible materials that exhibit biological response and material characteristics substantially the same as biocompatible metals, such as for example composite materials.

[0003] Conventional endoluminal stents, stent-grafts and covered stents are frequently used after a procedure which dilitates an occluded, obstructed or diseased anatomical passageway to provide structural support and maintain the patency of the anatomical passageway. An example of this is the post-angioplasty use of intravascular stents to provide a structural support for a blood vessel and reduce the incidence of restenosis. A principal, but non-limiting, example of the present invention are endovascular stents which are introduced to a site of disease or trauma within the body's vasculature from an introductory location remote from the disease or trauma site using an introductory catheter, passed through the vasculature communicating between the remote introductory location and the disease or trauma site, and released from the introductory catheter at the disease or trauma site to maintain patency of the blood vessel at the site of disease or trauma. Stent-grafts are delivered and deployed under similar circumstances and are utilized to maintain patency of an anatomic passageway, for example, by reducing restenosis following angioplasty, or when used to exclude an aneurysm, such as in aortic aneurysm exclusion applications.

[0004] While the use of endoluminal stents has successfully decreased the rate of restenosis in angioplasty patients, it has been found that a significant restenosis rate continues to exist in spite of the use of endoluminal stents. It is generally believed that the post-stenting restenosis rate is due, in major part, to the non-regrowth of the endothelial layer over the stent and the incidence of smooth muscle cell-related neointimal growth on the luminal surfaces of the stent. Injury to the endothelium, the natural nonthrombogenic lining of the arterial lumen, is a significant factor contributing to restenosis at the situs of a stent. Endothelial loss exposes thrombogenic arterial wall proteins, which, along with the generally thrombogenic nature of many prosthetic materials, such as stainless steel, titanium, tantalum, Nitinol, etc. customarily used in manufacturing stents, initiates platelet deposition and activation of the coagulation cascade, which results in thrombus formation, ranging from partial covering of the luminal surface of the stent to an occlusive thrombus. Additionally, endothelial loss at the site of the stent has been implicated in the development of neointimal hyperplasia at the stent situs. Accordingly, rapid re-endothelialization of the arterial wall with concomitant endothelialization of the body fluid or blood contacting surfaces of the implanted device is considered critical for maintaining vasculature patency and preventing low-flow thrombosis. [0005] At present, most endoluminal stents are manufactured of metals that fail to promote redevelopment of a healthy endothelium and/or are known to be thrombogenic. In order to increase the healing and promote endothelialization, while maintaining sufficient dimensional profiles for catheter delivery, most stents minimize the metal surface area that contacts blood. Thus, in order to reduce the thrombogenic response to stent implantation, as well as reduce the formation of neointimal hyperplasia, it would be advantageous to increase the rate at which endothelial cells form endothelium proximal and distal to the stent situs, migrate onto and provide endothelial coverage of the luminal surface of the stent which is in contact with blood flow through the vasculature.

[0006] Current stent-grafts and covered stents are essentially endoluminal stents with a discrete covering on either or both of the luminal and abluminal surfaces of the stent that occludes the open spaces, or interstices, between adjacent structural members of the endoluminal stent. It is known in the art to fabricate stent-grafts by covering the stent with endogenous vein or a synthetic material, such as woven polyester known as DACRON, or with expanded polytetrafluoroethylene. Additionally, it is known in the art to cover the stent with a biological material, such as a xenograft or collagen. A primary purpose for covering stents with grafts is to reduce the thrombogenic effect of the stent material. However, the use of conventional graft materials has not proven to be a complete solution to enhancing the healing response of conventional stents. [0007] U.S. Patent No. 6,312,463 describes a variation of a prosthesis that is a thin- walled coiled sheet having temperature-activated shape memory properties. The tubular element is supported by a support element that includes a plurality of struts. The tubular element is described as a thin- walled sheet preferably having of a coiled-sheet configuration with overlapping inner and outer sections.

[0008] There still remains a need in the art for an all-metal thin-film endoluminal device that provides a structural component to support an endoluminal wall and a covering component that covers the structural component, is biocompatible and prevents or limits the occurrence of restenosis. [0009] The present invention also relates to a method for physical vapor deposition

(PVD) of nickel-titanium alloys by sputter deposition in which several process parameters are controlled to achieve the inventive high-strength deposited nitinol films and the inventive graft materials. It has been found desirable control the energy of particles emitted from the target as they arrive at the substrate surface. One process parameter, in particular, that has been found to contribute significantly to producing the inventive high-strength nitinol films is the mean free path of particles emitted during sputtering of the sputter deposition target must be greater than about one-half the distance of the spatial separation between the target and the substrate. This condition is set by the requirement that the kinetic energy of the particles that are deposited must be much greater than the thermal energy in order to promote non- columnar film growth. This condition of the arrival of energetic particles to the substrate can be fulfilled also in other deposition methods, such as ion beam deposition and laser ablation, for example, hence the inventive method can be practiced by using other methods than sputtering. Control of other deposition process parameters has also been found to influence the strength characteristics of the resulting deposited film, including, employing a hollow cathode dc magnetron, controlled heating of the target, controlling the base pressure and working gas quality to avoid oxygen contamination of the depositing film, controlling the deposition pressure, controlling the surface roughness of the deposition substrate, controlling the composition of the substrate to avoid diffusion contamination into the depositing nitinol, and applying a negative bias voltage to the substrate. [0010] In the metallurgic arts, it is known that nickel-titanium alloys having nearly stoichometric 50-50 atomic percent nickel and titanium exhibit SME and are superelastic above certain temperatures. It is also known that ternary alloys that contain mostly nickel and titanium but also contain other components such as copper, chromium, tantalum, zirconium, or other metals also often exhibit SME. Similarly, nickel and titanium-based quaternary or more complex alloys can exhibit the SME. As used in the art, and as used in this application, the term "nickel-titanium alloy" is intended to include binary, ternary and quaternary alloys containing nickel and titanium that exhibit shape memory effect.

[0011] SME nitinol alloys may be manufactured both by conventional metallurgy and by vacuum deposition (See, e.g., U.S. Pat. No. 5,061,914). It has been found that vacuum deposition fabrication offers the possible advantage of readily adding alloying elements to produce a large variety of alloy films having a wide variety of transition temperatures. Heretofore, however, vacuum deposited films have exhibited inferior mechanical properties when compared with similar articles fabricated by conventional metallurgy. For puφoses of this application, those materials fabricated by conventional metallurgical methods will be referred to as "wrought nitinol" or "wrought nickel-titanium alloys." This difference in mechanical properties between wrought nitinol materials and vacuum deposited nitinol materials significantly limits the usefulness of vacuum deposited nitinol films. Some of the most appealing potential applications of nitinol films include micro-electro-mechanical (MEMS) devices and medical devices, such as endoluminal stents. However, since its inception over ten years ago, virtually no vacuum deposited thin film nitinol devices have been commercially marketed because of their insufficient strength relative to similar devices fabricated from wrought nitinol.

[0012] Shape memory and superelastic nitinol materials undergo a reversible phase transition between martensitic (M) and austenitic (A) phases. It is this property that makes use of nitinol materials especially desirable in certain applications, including medical devices, microelectronic sensor devices or the like. The M phase is stable at lower temperatures and/or high stresses, and the A phase is stable at higher temperatures and/or lower stresses. One of the most important characteristics of nitinol is the M to A transition temperature. This transition occurs within a range between A_s (start) and A_f (finish). The transition process is endothermic and may be characterized by the heat effect, ΔH and by the A_p temperature where, for a given rate of heating, the transition heat effect is maximum.

[0013] Wrought nitinol is produced by vacuum melting ingots. This method results in a nitinol material having the same transition temperature as the nitinol ingot, termed the "ingot A_p." The ingot A_p depends on the stoichiometry of nickel and titanium and the ingot, and may be between -50°C and 100°C. The ingot A_p is lower where there is excess nickel, i.e., greater than 50 at. %, and higher when the alloy contains excess titanium, i.e., more than 50 at. % Ti. Ingots are processed by shaping into sheets or tubes for further use in the industries such as the medical device industry. Particular end applications of nitinol materials require particular transition temperature values. However, ingots with a range of different A_p values are not available for each application. In order to address this difficulty in available ingots, a method called precipitation annealing is employed in order to adjust the A_p value of a given product. [0014] Precipitation annealing typically involves annealing nitinol at temperatures between 200-500°C for 10-180 min., then allowing the material to cool at a controlled cooling rate or by quenching at a temperature below about 200°C. As a result of precipitation annealing, the excess component in the ingot, either Ni or Ti, will precipitate out from the crystal structure and form inclusions such as, for example, Ni₃Ti₂, NiTi₂, or the like. These inclusions constitute a separate phase along the nitinol grain boundaries or within the nitinol grains and are termed "precipitates."

[0015] The degree to which precipitate formation is necessary depends upon the relationship between the ingot A_p and the desired device A_p. Currently, manufacturer of a particular nitinol device, such a medical device manufacturer, e.g., a stent manufacturer, will purchase raw material, such as sheets or tubes from a nitinol ingot fabricator. The ingots from which the raw material is fabricated, will, in all likelihood vary in their material constitution and A_p value during the life of the device manufacturer's product line. Thus, in order to achieve a desired device A_p> device manufacturers must adjust the precipitation- annealing step for the given ingot A_p of any particular batch of raw material received from the ingot fabricator. The inevitable result of this need to engage in precipitation annealing to adjust for the ingot A_p is that there is variability in the amount of precipitates within the same device product line depending on the starting raw material. Because control of the ingot A_p values ingot to ingot is extremely difficult, this variability is present even where ingots are made by the same fabricator. [0016] Precipitates in metals have implications for the mechanical, corrosion, and i fatigue properties. Precipitates tend to constrain slip plane movements during plastic deformation and hence the concept of precipitation hardening of metals. Hardening, if it is desirable, can also be achieved using cold working in traditional metallurgy. In the case of thin film metallurgy, hardening may be controlled by the deposition parameters through controlling grain size, which is a function of substrate temperature and growth rate, among others. So, even if hardening is desirable, it can be achieved by alternative methods, without resorting to induced precipitate formation. Concerning other mechanical properties, precipitates tend to make materials more brittle, and decrease fatigue life. This is caused by local strain fields that arise around the precipitates, which are situated incongruently between the grains of the material. Precipitates may initiate micro-cracks along the grain boundaries and are known to contribute to intergranular failure. With regard to corrosion properties, precipitates may have detrimental effects in two ways: (i) the mentioned strain field and the related micro-cracks may increase the effective surface area exposed to corrosive environment and (ii) local micro-elements (corrosion pairs) may be formed by the precipitate and the surrounding nitinol matrix.

[0017] It is known that nitinol can be made not only using the traditional metallurgical approach described in the previous paragraphs but also using film deposition technologies. Inherent in this approach, the producer of nitinol can have as good or better a control of the A_p transition temperature than in the production of ingots. Deposition can provide fine adjustment of the nitinol chemical composition and thus to eliminate or reduce precipitation thereby reducing hardness, and consequently reducing the plateau stress, and improving the strength at the same time. However, deposition technologies are not commonly used in applications where the composition control must be within about 0.1 at% in order to control the transition temperature within about 10°C.

[0018] The most common deposition method for producing nitinol is dc sputter deposition. We will describe the invention in terms of a distinct form of dc sputter deposition, i.e., using the example of hollow cathode (HC) dc magnetron sputtering (See, e.g., E. Kay, Cylindrical Cathode Sputtering Apparatus Including Means for Establishing a Quadrupole Magnetic Field Transverse of the Discharge, US Pat. No. 3,354,074, Sept. 16, 1963). However, the skilled in the deposition art will see that the principles outlined are applicable for a wide range of deposition methods.

[0019] Typically, sputter deposited nitinol is more Ni-rich than the sputtering target employed. The reasons for this are complex and without a good understanding of these reasons, various researchers have employed a variety of remedies. These include (i) the addition of extra Ti to the target in form of Ti sheets placed on the target, or some similar approach, and (ii) allowing the target to reach high temperatures, whereby, as experience shows, the Ti content of the films is enhanced. It is an object of the present invention to provide a method of adjusting the Ti content (Ni to Ti atomic ratio) of deposited nitinol films using the above and the adjustment of sputtering parameters. It is a further objective of the present invention to produce vacuum deposited nitinol thin films that are deposited in their martensite phase and behave martensitically in vivo, or are deposited in their austenite phase and behave austenitically in vivo, or are deposited in their martensite phase and behave austenitically in vivo. Those materials that are deposited in the martensite phase and behave martensitically in vivo are deposited with an atomic stoichiometry such that the A_s value of the film is above body temperature. Those materials that are deposited in their austenite phase and behave austenitically in vivo are deposited with an atomic stoichiometry such that the A_s values are below both the ambient environmental temperature and below body temperature. Finally, those materials that are deposited in their martensite phase and behave austenitically in vivo are deposited with an atomic stoichiometry such that the A_s values are typically above the ambient environmental temperature, but below body temperature. An important aspect of these inventive vacuum deposited films is that the material, as deposited, exhibits the desired A_s value without the need for heat setting by annealing to adjust the transition temperature of the material.

[0020] Vacuum deposition of nitinol provides the additional advantage over wrought nitinol in that high Ni content material can easily be produced. The manufacturing of high Ni content wrought material is impeded by its extreme abrasiveness and toughness that makes extrusion, rolling and the like not feasible. In particular, the production of devices from wrought nitinol with A_P<-20°C is very difficult if not impossible. (See, e.g., . D. Hodgson and S. Russell: "Nitinol melting, manufacture and fabrication" in Minimally Invasive Therapy & Allied Technologies, Vol. 9 No 2 March 2000 pp 61-65). Further advantages of vacuum deposition include (1) the ability of making thin walled tubes with high wall thickness uniformity, (2) the ability of making thin sheets with high thickness uniformity, (3) the ability of making objects with complex shapes, for example tubes with variable diameter along the length, such as funnel and balloon shapes, (4) better control over the material purity (5) control over material composition in terms of adding minor alloying elements such as, for example Ta in order to improve radio opacity.

[0021] Typically, sputter deposited nitinol has inferior mechanical properties as compared to wrought nitinol. This inferiority is manifest most clearly in the ultimate strength. The ultimate strength of the nitinol material described by Johnson (A. D. Johnson et al. US Patent Application 2001/0039449) appears from Figure 3 in the published application to be approximately 500 MPa.

[0022] Mechanical properties of metals typically depend on their microstructure. Specifically, microstructure of deposited metal films consists of two main types of features: (i) the grain structure with the grain boundaries and precipitates both intragranular and intergranular, and (ii) texture such as columns. The grain structure is important because it determines the fundamental mechanical properties. Amorphous metals, i.e., those metals having no defined grain structures or grains that are too small to be detected by X-ray diffraction, are known to be very hard and brittle. Similarly, crystalline metals having very small grain sizes are also known to be quite brittle, but become more ductile as the grain size increases. When the grain size becomes very large, the metals lack strength and have low elastic limits. Thus, achieving a correct grain size plays a significant aspect of any metal fabrication technology. It is known that for wrought nitinol materials it is desirable to have grain sizes typically within the range of 0.1-10 μm in order to have practical mechanical properties.

[0023] In order to deposit nitinol films having thicknesses on the order of 0.1 - 25 μm, high deposition rates are typically employed. At such higher deposition rates, the resultant nitinol film develops generally columnar grain morphology. This columnar morphology is significant because it imparts features similar to grain boundaries, yet the columnar features traverse substantially the entire thickness of the resulting film. Like typical grain boundaries, the columnar grain morphology creates defect regions that are weaker than other regions of the film, and contaminants and precipitates may segregate into these defect regions. It is necessary, therefore, to avoid columnar grain growth during vacuum deposition in order to obtain nitinol films with higher mechanical strengths. Columnar growth results from the combination of the following factors: (i) low surface diffusion rate, (ii) expressed surface features, such as roughness, and (iii) directional deposition See, e.g., G. S. Bales, R. Bruinsma, E. A. Eklund, R. P. U. Karunasiri, J. Rudnick, A. Zangwill, Growth and Erosion of Thin Solid Films, Science, Vol. 249 p. 264-268, July 1990). It is an object of this invention to provide a method of choosing deposition parameters that result in nitinol film growth process without columnar growth.

Summary of the Invention [0024] An aspect of the present invention provides an implantable medical device that includes a microporous metal thin film covering comprised of a metallic or pseudometallic material and an underlying structural support made of a metallic or pseudometallic material. The microporous metal thin film covering is preferably physically attached to the underlying structural support, preferably by welding, suturing, or other commonly known methods of attachment at particular interfacial points. In a preferred aspect of the present invention, both the microporous metal thin film covering and the underlying structural support are fabricated from metallic or pseudometallic materials having shape memory and/or superelastic properties that are vacuum deposited without the need for precipitation annealing to set the transition temperature. More preferably, the metal used to fabricate the inventive implantable endoluminal graft is Nitinol. The underlying structural support, without the microporous metal thin film covering, is similar to implantable devices known as a "stents." The underlying structural support can assume any commonly known geometry in the art that possess requisite hoop strength, circumferential compliance and longitudinal flexibility for both endoluminal delivery and acting as an in vivo prosthesis. In a preferred embodiment, the structural support element adopts a geometry that includes at least a pair of cylindrical elements and interconnecting members that join adjacent cylindrical elements at nearly identical angular points along the circumference of the cylindrical elements.

[0025] In another aspect of the present invention, an implantable graft includes a microporous metal thin film covering comprised of a metallic material which has shape memory and/or pseudoelastic properties and a structural support element underlying the microporous metal thin film covering. "Pseudoelastic properties" is used herein to refer to the ability of the metallic material to undergo "pseudoelastic deformation". In a preferred aspect, the structural support element has shape memory properties that allow the structural support element to undergo a phase transition from martensite to austenite phase at body temperature. During this phase transition, the structural support element self-expands from an initial, delivery diameter to an enlarged expanded diameter for its intended in vivo use. The shape memory expansion of the structural support element exerts a radially expansive force upon the microporous metal thin film covering, thereby causing the microporous metal thin film to radially expand with the structural support element. While the expansion of the microporous metal thin film appears to be plastic, because the microporous metal thin film is a shape memory material, the expansion is actually fully recoverable above the transition temperature of the material, and is, therefore, "pseudoplastic".

[0026] In still another aspect of the present invention, an implantable endoluminal graft is comprised of a microporous metal thin film covering comprised of a shape memory alloy having an austenite phase transition temperature, A_s, greater than 37° C and a structural support element underlying the microporous metal thin film covering that is comprised of a shape memory alloy that has an austenite phase transition temperature less than 0° C. Thus, in both the delivery diameter and the implanted expanded diameter, the microporous metal thin film remains in a martensite state, while the structural element undergoes a phase transition from martensite to austenite at body temperature.

[0027] Another aspect of the present invention is an implantable endoluminal graft wherein the structural support element is physically attached to the microporous metal thin film covering at least one point of contact between the microporous metal thin film covering and the structural support element. Preferably, the at least one point of contact is located at either near a proximal end or distal end of the microporous metal thin film covering and corresponding end of the structural support element. Even more preferably, the at least one point of contact is located at near a distal end of the microporous metal thin film covering and structural support element. The physical attachment of the structural support element to the microporous metal thin film covering is accomplished by using a spot weld, a suture, adhesive, or other means of physically joining the two elements. Preferably, the attachment is accomplished using a spot weld.

[0028] In another aspect of the present invention, the implantable endoluminal graft includes a structural support element comprised of a cylindrical element having a sinusoidal pattern with alternating peaks and valleys. Furthermore, interconnecting members join adjacent cylindrical elements either peak-to-peak or valley-to-valley. In accordance with a preferred embodiment of the invention, the structural elements that form each of the cylindrical elements preferably have a width that narrows at and near the apices of the peaks and valleys to accommodate expansion of each cylindrical element.

[0029] In another aspect of the present invention, the implantable endoluminal graft includes a structural support element comprised of a cell that is defined by adjacent interconnecting members and sections of the pair of cylindrical elements connecting the adjacent interconnecting members, the cell comprised of a pair of peaks or a pair of valleys. Similar to the cylindrical elements, it is preferable that each opposing end of each interconnecting member have a width that is narrower than the remaining intermediate section of the interconnecting member. In this manner, the narrower sections of the interconnection members and of the cylindrical elements are regions that experience higher strain during expansion of the structural support element. [0030] In another aspect of the present invention, the implantable endoluminal graft includes a microporous metal thin film covering comprised of a uniform pattern of openings throughout the surface of the microporous metal thin film covering. The openings can be selected from common geometric shapes including a circle, triangle, ellipsoid, diamond, star, clover, rectangle, square, or straight or curved slots. [0031] The structural support member may consist of any type of structural member and is preferably generally tubular in configuration, and has an inner or luminal wall and an outer or abluminal wall and a central lumen passing along the longitudinal axis of the structural support member. The structural support member may be comprised of a wide variety of geometric configurations and constructions, as are known in the art. For example, -li¬

the structural support member may assume a balloon expandable slotted configuration of U.S. Patent Nos. 4,733,665, 4,739,762, 4,776,337 or 5,102,417 or the structural support member may be configured as a plurality of self-expanding interwoven wire members or it may assume any of the wall geometries disclosed in Serruys, P.W., Kutryk, M.J.B., Handbook of Coronary Stents. 3^rd Ed. (2000). Each of the structural support member designs, structural support member materials, structural support member material characteristics, e.g., balloon expandable, self-expanding by spring tension of the material, self-expanding by shape memory properties of the structural support member material, or self-expanding by superelastic properties of the structural support member material are well known to one of ordinary skill in the art and may be used with the implantable graft of the present invention. [0032] An aspect of the present invention is the fabrication of the implantable endoluminal graft using various techniques that can create a blood contact surface that has controlled heterogeneities therein. More particularly, this aspect of the present invention provides an implantable endoluminal graft that is made of a material having controlled heterogeneities in its atomic profile, material composition, grain composition, grain phase, grain size, or surface topography, along the blood flow surface of the implantable endoluminal graft and which has a predefined atomic stoichiometry such that the deposited material exhibits a predetermined transition temperature without post-deposition annealing. [0033] Another aspect of the present invention is a method for making the implantable graft which employs vacuum deposition methodologies, such as those employed in the microelectronics fabrication arts. For example sputtering, physical vapor deposition, ion beam-assisted evaporative deposition or the like may be used to create the microporous metal thin film covering and the structural support member components of the implantable graft device. In ion beam-assisted evaporative deposition it is preferable to employ dual and simultaneous thermal electron beam evaporation with simultaneous ion bombardment of the material being deposited using an inert gas, such as argon, xenon, nitrogen or neon. Bombardment with inert gas ions during deposition serves to reduce void content by increasing the atomic packing density in the deposited material. The reduced void content in the deposited material allows the mechanical properties of that deposited material to be similar to the bulk material properties. Deposition rates up to 20 nm/sec are achievable using ion beam-assisted evaporative deposition techniques.

[0034] When sputtering techniques are employed, a 200-micron thick stainless steel film may be deposited within about four hours of deposition time. With the sputtering technique, it is preferable to employ a cylindrical sputtering target, a single circumferential source that concentrically surrounds the substrate that is held in a coaxial position within the source.

[0035] During deposition, the chamber pressure, the deposition pressure and the partial pressure of the process gases are controlled to optimize deposition of the desired species onto the substrate. As is known in the microelectronic fabrication, nano-fabrication and vacuum coating arts, both the reactive and non-reactive gases are controlled and the inert or non-reactive gaseous species introduced into the deposition chamber is typically argon. The substrate may be either stationary or moveable; either rotated about its longitudinal axis, moved in an X-Y plane, planatarily or rotationally moved within the deposition chamber to facilitate deposition or patterning of the deposited material onto the substrate. The deposited material maybe deposited either as a uniform solid film onto the substrate, or patterned by (a) imparting either a positive or negative pattern onto the substrate, such as by etching or photolithography techniques applied to the substrate surface to create a positive or negative image of the desired pattern or (b) using a mask or set of masks which are either stationary or moveable relative to the substrate to define the pattern applied to the substrate. Patterning may be employed to achieve complex finished geometries of the resultant structural supports or microporous metal thin film covering, both in the context of spatial orientation of patterns of regions of relative thickness and thinness, such as by varying the thickness of the film over its length to impart different mechanical characteristics under different delivery, deployment or in vivo environmental conditions.

[0036] The device may be removed from the substrate after device formation by any of a variety of methods. For example, the substrate may be removed by chemical means, such as etching or dissolution, by ablation, by machining or by ultrasonic energy. Alternatively, a sacrificial layer of a material, such as carbon, aluminum or organic based materials, such as photoresists, may be deposited intermediate the substrate and the structural support member and the sacrificial layer removed by melting, chemical means, ablation, machining or other suitable means to free the structural support member from the substrate. [0037] The resulting device may then be subjected to post-deposition processing to modify the crystalline structure, such as by annealing, or to modify the surface topography, such as by etching to expose a heterogeneous surface of the device.

[0038] Alternate deposition processes which may be employed to form the structural support member in accordance with the present invention are cathodic arc, laser ablation, and direct ion beam deposition. As known in the metal fabrication arts, the crystalline structure of the deposited film affects the mechanical properties of the deposited film. These mechanical properties of the deposited film may be modified by post-process treatment, such as by, for example, annealing.

[0039] Materials to make the implantable endoluminal graft are chosen for their biocompatibility, mechanical properties, i.e., tensile strength, yield strength, and their ease of deposition include, without limitation, the following: elemental titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, such as zirconium-titanium-tantalum alloys, nitinol, and stainless steel.

[0040] The implantable endoluminal graft device of the present invention is formed entirely of metal or pseudometal material that exhibits improved endothelialization and healing response as compared to that associated with using conventional synthetic polymeric graft materials.

[0041] In accordance with the method and material of the present invention vacuum deposited nitinol films having grain sizes within the range of 0.1-1 μm have been produced and exhibit optimal mechanical properties. Thin walled nitinol tubes, such as tubes with diameters in the 1-16 mm range have been successfully manufactured using the inventive technology with wall thicknesses of about 3-20 micron with wall thickness uniformity of about <10%. Sheets have been formed from tubes by cutting along the longitudinal axis of the tube, however, such sheets are readily fabricated in planar vacuum deposition systems. Prototype angioplasty balloons capable of being repeatedly inflated at pressures of several Atm have also been fabricated using the inventive methodology. The method of the present invention avoids using lubricants necessary in fabrication using cold working processes that contaminate heavily cold worked materials such as small diameter tubes like those used for cutting coronary stents. Finally, nitinol tubes having about 5% Ta added have been produced using the inventive method.

[0042] It is a principle objective of the present invention to provide high strength deposited nitinol materials. In particular, it is an object of the present invention to provide high strength vacuum deposited nitinol films that are useful in medical, mechanical and electronic applications. A further objective of the present invention is to provide a method of making the high strength nitinol materials. Additionally, in view of the difficulties in maintaining desired A_p values, the present invention provides a method of forming nitinol materials having desired transition temperature values without employing precipitation annealing. [0043] The present invention provides high strength nitinol materials that may be used either as precursors or finished products with improved mechanical strength, fatigue and corrosion resistance when compared to wrought nitinol materials. The inventive vacuum deposition process is essentially a vacuum deposition process in which Ni and Ti atoms are co-deposited from a target or targets onto a substrate where they form nitinol alloy. The inventive process is carried out with control over the atomic ratio of the resulting nitinol film, such that no precipitation annealing is required in order to tailor or adjust the A_p transition temperature of the deposited film. The individual details of the inventive deposition process, including the fabrication of the nitinol target, the target temperature, the substrate surface roughness, application of a voltage bias, and other deposition parameters are chosen such that the resulting nitinol film has the chemical purity and crystalline microstructure necessary to produce high mechanical strength.

[0044] The method of the present invention entails vacuum depositing under conditions where the sputtering target and substrate are spatially separated from one another such that the mean free paths of the particles emitted from the target is greater than about half the distance between the target and the substrate. According to the best mode known at the present time to the inventors, vacuum deposition is conducted in a hollow cathode dc magnetron, in which the sputtering target is partially or fully thermally decoupled or insulated from a cooled cathode in the sputtering reactor. The target temperature is regulated by the applied sputtering power. The target composition is selected according to the desired transition temperature and the nitinol target may be modified by adjusting the relative amounts of Ni or Ti in the target by welding Ni or Ti wires to the target surface. Alternatively, separate Ni and Ti targets may be employed, with the ratio of Ni target to Ti target being adjusted to achieve the desired transition temperature in the deposited nitinol film. The applied sputtering power is chosen such that the target temperature is high enough to produce a desired amount of Ti segregation, as determined from the Ti content of the resulting nitinol films. The base pressure and Ar gas quality are selected to avoid oxygen contamination of the nitinol film. The deposition pressure and the target-to-substrate distance, also known as the "throw distance" are sufficiently small to minimize atomic scattering of the Ni and Ti atoms within the plasma. Additionally, the surface roughness of the substrate is controlled so that it is substantially uniformly smooth. Additionally, the substrate temperature is selected to be sufficiently high so that at a given selected deposition rate the deposited nitinol material will be crystalline. The substrate temperature is preferably balanced to also be sufficiently low in order to avoid diffusion contamination from the substrate into the deposited nitinol. The substrate is preferably negatively biased to a bias voltage selected to be sufficiently high in order to atomically compact the deposited nitinol film, yet sufficiently low in order to avoid substantial deleterious effects such as re-sputtering from the substrate or Ar implantation. [0045] Thus, by stringently controlling the parameters of sputter deposition, the method of the present invention achieves a balance of process parameters that yield a nitinol film having improved strength and predictable and defined A_p values without the need for precipitation annealing to adjust or attenuate the transition temperature of the finished nitinol material. Brief Description of the Figures

[0046] Figure 1 is a plan view of an embodiment of the implantable device its delivery diameter.

[0047] Figure 2 is a plan view of an embodiment of the implantable device in its expanded or intended in vivo diameter. [0048] Figure 3 is a plan view of a structural support element of a preferred embodiment of the implantable endoluminal device while in an expanded diameter.

[0049] Figure 3 A is a fragmentary plan view of an alternate embodiment of an apex portion of a structural support member in accordance with the inventive implantable endoluminal device. [0050] Figure 4 is an exploded plan view of a microporous metal thin film covering of an embodiment of the implantable endoluminal device while in an expanded diameter.

[0051] Figure 5 is a plan view of a structural support element of an alternative embodiment of the inventive implantable endoluminal device.

[0052] Figure 6 is a plan view of a pattern of openings for a microporous metal thin film covering in accordance with a preferred embodiment of the present invention.

[0053] Figure 7 is a plan view of a section of a microporous metal thin film covering of an embodiment of the present invention in a curved configuration depicting compliance of the microporous metal thin film covering.

[0054] Figure 8 is a plan view of a microporous metal thin film covering of an alternative embodiment of the present invention shown in unexpanded-longitudinally expanded-unexpanded regions.

[0055] Figure 9 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention. [0056] Figure 10 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0057] Figure 11 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention. [0058] Figure 12 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0059] Figure 13 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0060] Figure 14 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0061] Figure 15 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0062] Figure 16 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention. [0063] Figure 17 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0064] Figure 18 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0065] Figure 19 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0066] Figure 20 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0067] Figure 21 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention. [0068] Figure 22 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0069] Figure 23 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0070] Figure 24 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0071] Figure 25 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention.

[0072] Figure 26 is a plan view of a pattern of openings for a microporous metal thin film covering of an alternative embodiment of the present invention. [0073] Figure 27 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft while in an expanded diameter.

[0074] Figure 28a and 28b are plan views of a structural support element of an alternative embodiment of the implantable endoluminal graft while in an expanded diameter with short and long interconnecting members, respectively.

[0075] Figure 29 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0076] Figure 30 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft. [0077] Figure 31 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0078] Figure 32 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0079] Figure 33 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0080] Figure 34 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0081] Figure 35 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft. [0082] Figure 36 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0083] Figure 37 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0084] Figure 38 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0085] Figure 39 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft.

[0086] Figure 40 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft. [0087] Figure 41 is a plan view of a structural support element of an alternative embodiment of the implantable endoluminal graft illustrating different patterns of the microporous openings in the microporous metal thin film coverings.

[0088] Figure 42 is a process flow diagram of inventive method for fabricating high- strength nitinol films. [0089] Figure 43 is a diagrammatic representation of the inventive cylindrical magnetron sputtering apparatus.

[0090] Figure 44 is an electron microprobe spectrum of the inventive nitinol film deposited by sputter deposition. [0091] Figure 45 is a Differential Scanning Calorimeter curve obtained from testing the inventive nitinol film.

[0092] Figure 46 is a graph depicting the stress-strain curve characteristic of the inventive nitinol film.

[0093] Figures 47A and 47B are scanning electron micrographs depicting a transverse cross-sectional view of a conventional (Fig. 47A) and the inventive (Fig. 47B) nitinol film.

[0094] Figure 48 is an X-ray diffraction pattern of the inventive nitinol film.

[0095] Figure 49 is a transmission electron micrograph obtained from the inventive nitinol film.

[0096] Figure 50 is an electron diffraction pattern obtained from the inventive nitinol film.

[0097] Figure 51 is a surface profilometer track obtained from testing the inventive nitinol film.

[0098] Figure 52 is a graph depicting the average flight distance of an atom between coplanar surfaces of a target and a substrate. [0099] Figure 53 is two dark field optical micrographs taken through a 100X objective of a 5μm nitinol film grown under conditions where energetic particles from the target were excluded from the substrate (Panel 53a) and admitted to the substrate (Panel 53(b).

[00100] Figure 54 is bright field optical micrograph taken through a 4X objective of a 5μm nitinol film depicting both rough and smooth regions on the surface of the film.

[00101] Figure 55 is a graph depicting the relationship between cathode voltage and working gas pressure at constant sputtering power.

[00102] Figure 56 is a graph depicting the relationship between working gas pressure and sputtering power for a constant cathode voltage.

Detailed Description of the Preferred Embodiments

[00103] The present invention includes an inventive high-strength shape memory and/or superelastic nitinol material as well as a process for fabricating the thin-film shape memory and/or superelastic nitinol materials, including the inventive graft material. The inventive material is characterized by having high mechanical strength and toughness exceeding that found in the art and does not require precipitation annealing to either shape set or set the transition temperature of the material. In accordance with the method of the present invention, the inventive nitinol materials may be produced for certain intended end-uses, such as MEMS and medical devices, using deposition technologies including but not limited to PVD, sputter deposition, plasma deposition, ion beam deposition or the like to form the film, and post-deposition use of etching, photolithography, machining, or ablation techniques to fashion the deposited film for an intended end-use. In addition to depositing shape memory nitinol materials in their martensite state and having A_s values below body temperature so that they transition to the austenite phase upon in vivo introduction, the method of the present invention may be employed to deposit nitinol materials in a martensite state having A_s values greater than body temperature so that these materials exhibit martensitic behavior in vivo. Alternatively, the method of the present invention may be employed to deposit nitinol materials in an austenite phase having an A_s value sufficiently low so as to behave completely austeniticly in vivo. A significant aspect of the method of the present invention, is that the method succeeds in depositing materials such that the stoichiometry of the nickel-titanium alloy is such that no heat setting is required to impart a desired transition temperature value, rather the materials as deposited using the invention method have predetermined transition temperature values imparted as a result of manipulation of the method parameters described. [00104] By employing vacuum deposition methodologies, one is able to form materials directly into a desired 2D or 3D geometry, e.g., planar, tubular, or multi-surfaced geometries. The common principle of the deposition processes is to take a material in a minimally processed form, such as pellets or thick foils (the source material) and atomize them. The term atomization is used here loosely to include forming atomic or molecular size particles, both charged and/or neutral and both comprised of a single atom and/or of a cluster of atoms. Atomization may be carried out using heat, as is the case in PVD, or using the effect of collisional processes, as in the case of sputter deposition, for example. The atoms or particles of the source material then deposit on a substrate or mandrel to form the desired material. In most cases, the deposited material is then either partially or completely removed from the substrate, to form the desired product.

[00105] Without limiting the scope of application of the present invention, the following are specific examples of products or devices which may be fabricated using the present invention: implantable nitinol stents, nitinol grafts, stent-graft devices in which either or both components are fabricated from the inventive nitinol material, general purpose seamless nitinol tubes, sheets, films or foils which may be, for example, employed as MEMs devices.

[00106] In accordance with the present invention, an implantable endoluminal graft is provided that is comprised of two main features: a microporous metal thin film covering and an underlying structural support member, which are physically connected to one another. The implantable endoluminal graft has a delivery profile that allows for uncomplicated entry and passage throughout an anatomical passageway, more particularly a vascular system. Additionally, the implantable endoluminal graft is formed from a shape memory material, preferably nitinol, which permits the graft to expand in vivo to support a lumen wall.

[00107] The term "pseudometal" and "pseudometallic material," as used herein, is defined as a biocompatible material which exhibits biological response and material characteristics substantially the same as biocompatible metals. Examples of pseudometallic materials include, for example, composite materials, ceramics, quartz, and borosilicate. Composite materials are composed of a matrix material reinforced with any of a variety of fibers made from ceramics, metals, or polymers. The reinforcing fibers are the primary load carriers of the material, with the matrix component transferring the load from fiber to fiber. Reinforcement of the matrix material may be achieved in a variety of ways. Fibers may be either continuous or discontinuous. Reinforcement may also be in the form of particles. Examples of composite materials include those made of carbon fibers, boron fibers, boron carbide fibers, carbon and graphite fibers, silicon carbide fibers, steel fibers, tungsten fibers, graphite/copper fibers, titanium and silicon carbide/titanium fibers. For purposes of the description of the invention where the inventive microporous thin film material is referred to as a microporous metal thin film, it will be understood to include both metal and pseudometallic materials.

[00108] The term "Elastic Deformation," as used herein, is defined as a deformation caused by an applied load that is completely recoverable upon removal of the applied load. The elastic limit of a traditional metal is typically less than 1% strain. [00109] The term "Plastic Deformation," as used herein, is defined as deformation caused by an applied load that cannot be completely recovered upon removal of the load because bonds have been broken.

[00110] The term "Pseudoelastic Deformation," as used herein, is defined as a deformation caused by an applied load that is completely recoverable upon removal of the load and the limit of which is characterized by being significantly larger than the elastic limit of a traditional metal (8% strain in the case of nitinol). This phenomenon is caused by a load or stress induced phase change that is reversible upon removal of the load.

[00111] The term "Pseudoplastic Deformation," as used herein, is defined as a deformation caused by an applied load that requires some other action besides load removal, such as the application of heat, for complete recovery of the defoπnation. In pseudoplastic deformations, bonds have not been broken but, instead, have been reoriented (detwinned in the case of martensitic nitinol).

[00112] A stress-strain curve for austenitic nitinol in which a sample is taken all the way to failure at a temperature above A_f (finish of Austenitic transformation) can be separated into the following regions: elastic deformation of austenite, pseudoelastic deformation of austenite to stress induced martensite, elastic deformation of the stress induced martensite, plastic deformation of the stress induced martensite and fracture. Removal of the load at any point before the onset of plastic deformation of the stress induced martensite will result in complete recovery of the deformation.

[00113] Nitinol is in the thermally induced martensite state if the material deformed at temperatures below M_f (finish of Martensitic transformation) and subsequently kept below A_s (onset of austenitic transformation) or restrained from recovering its programmed shape above A_s. A stress-strain curve for martensitic nitinol in which a sample is taken all the way to failure at a temperature above below A_s can be separated into the following regions: elastic deformation of thermally induced martensite, pseudoplastic deformation of thermally induced martensite via detwinning, elastic deformation of the detwinned thermally induced martensite, plastic deformation of the detwinned thermally induced martensite and fracture. Removal of the load at any point before the onset of plastic deformation of the detwinned thermally induced martensite will result in complete recovery of the deformation when heated above A_f.

[00114] In a preferred embodiment of the present invention, the A_s temperature of the NiTi thin film microporous metal thin film covering is above body temperature. The microporous metal thin film covering is in a thermally induced martensite phase at its delivery diameter in a delivery catheter and, because the microporous metal thin film covering is approximately the same diameter as the ID of the catheter sheath, the microporous metal thin film covering experiences virtually no deformation while in the catheter. Upon delivery, the microporous metal thin film covering experiences a pseudoplastic radial deformation under the influence of shape memory expansion of the structural support.

[00115] In a preferred embodiment of the present invention, the A_f temperature of the NiTi structural support element is below body temperature. The structural support element is brought to a temperature below M_f and loaded into the catheter at a temperature below A_s such that the structural support element is in a thermally induced martensite phase before deformation from to the delivery diameter occurs. The structural support element is psueoplastically deformed during crimping and is considered to be in the pseudoplastically deformed, thermally induced martensite phase until deployment in the body by removing the constraining force at a temperature above Af.

[00116] Concerning the fabrication and physical characteristic of the present invention, it is important to contemplate the blood protein interaction with surfaces of endoluminal devices because it appears to be an initial step in a chain of events leading to tissue incorporation of the endovascular device, and eventually to re-endothelialization along the surface of the device. An aspect of the present invention is based, in part, upon the relationship between surface energy of the material used to make the endoluminal device and protein adsorption at the surface of the endoluminal device. It has been found that a relationship exists between surface free energy and protein adsorption on metals commonly used in fabrication of endoluminal devices. In addition, specific electrostatic forces resident on the surface of metal endoluminal stents have been found to influence blood interactions with the graft surface and the vascular wall.

[00117] Another important factor to consider is electrostatic forces, which play a significant role in limiting interaction between the natural endothelial lining of the vasculature, which is highly electronegative, and a majority of plasma proteins and blood borne cells that also bear a net electronegative charge. Upon introduction of an implantable endoluminal device into the vasculature, the electrostatic surface charge on surfaces of the thin film covering and the structural support which are in contact with blood, will also interact with plasma proteins, blood borne cells and the healthy endothelial lining at the site of the device. Current implantable endoluminal devices are typically fabricated of one of the following metals: 316L stainless steel, nitinol, gold, tantalum or titanium. These examples exhibit poor endothelialization in cases where implanted endoluminal devices are made of these materials and result in restenosis.

[00118] In order to determine the cause for failure of re-endothelialization, the surface properties of metals commonly used in endoluminal devices, including grafts, stents and stent-grafts, were evaluated for free energy and electrostatic charge. The relationship between free energy at the surface of an endoluminal device material and protein adsorption was evaluated by preparing five separate samples as flat, square lxl cm pieces: electropolished 316L stainless steel, nitinol with two different surface preparations: electropolished and electropolished/heat-treated, gold, tantalum and titanium. The electrostatic charges at the surface of each of these metals were evaluated by atomic force microscopy (AFM) to examine the possible electrostatic heterogeneity of the device's metal surface.

[00119] In addition, the microtopology of the endoluminal device material surface will have an effect on protein binding, both during initial protein binding to the material surface as well as during the cascade of protein binding necessary for endothelialization of the material surface. Thus, surface features such as homogeneous atomic profile and material grain size will affect both primary binding of a protein, whether a blood borne protein or a cellular surface protein, at, for example, hydrophobic regions of the protein and affect secondary binding of the hydrophilic binding region of the protein upon protein bending and attraction to surface regions of the material.

Surface Free Energy Testing

[00120] Five samples of metals and metal alloys commonly used to make stents were prepared as flat, square 1 x 1 cm pieces: electropolished 316L stainless steel, nitinol with two different surface preparations: electropolished and electropolished/heat-treated, gold, tantalum and titanium. All sample pieces underwent a standardized 5 step ultrasonic cleaning process as follows: initial bath in detergent (20% Extran 1000, VWR Science, West Chester, P.C.) followed by distilled water rinse, methanol rinse, acetone rinse and distilled water rinse, in sequence.

[00121] Each of the five samples were exposed to single protein solutions at physiological concentrations of albumin (Armour Pharmaceutical Company, Kankakee, IL), fibrinogen (Sigma Chemical Co., St. Louis, MO) and fibronectin (ICN Biomedicals, Aurora, OH). Each protein solution was spiked with a low concentration of the corresponding radiolabeled protein as follows: I¹²⁵ albumin (Amersham Pharmacia biotech, Arlington

Heights, IL), I¹²⁵ fibrinogen or I¹²⁵ fibronectin (ICN Pharmaceuticals, Inc., Irvine, CA). The estimated overall activity of the solutions was 0.64 x 10^δ dpm/ml. Static protein adsorption was determined by immersing the material pieces in the iodinated protein solution for 2 hours at 37 D C. After removal from the solution, the activity on the specimens was assessed in an automated well counter. Then, each piece was rinsed in phosphate buffered saline solution for 24 hours at 37D C and the activity of the remaining protein on the surface was reassessed. Each experiment was repeated three times.

[00122] Surface energy of all materials was determined by the advancing contact angle measurement using a video contact angle system (VCAS 2500 XE, AST systems, Billerica, MA.) and calculated by the harmonic mean method. Water, formamide and xylene were used to computer total surface energy and the polar and dispersive components. Ten videocaptures per second of the advancing fluid droplet/solid interface were obtained for water and formamide and 65 captures per second for xylene. All experiments were repeated 4 times.

Results of Surface Free Energy Testing

[00123] Total surface energy of 316L stainless steel, electropolished (ep) nitinol, electropolished and heat treated (epht) nitinol, gold, tantalum and titanium, ranged from 32.8 dyne/cm for ep nitinol to 64.6 dyne/cm or 316L stainless steel with an average of 43.94.8 dyne/cm. The total surface energies for each metal tested is depicted in Figure 2. The polar and dispersive, or non-polar, components of the total surface energy of each metal are depicted in Figure 3, with the non-polar component being the largest with an average polar/non-polar ratio of 0.210.07. [00124] Protein binding was found to be relatively uniform for all metal surfaces studied. Of the three proteins tested, albumin adsorption was lower than fibronectin on all metals, and also lower than fibrinogen except for adsorption on gold and titanium, as illustrated in Figure 4. The fraction of protein removed after elution was higher for albumin than for either fibrinogen or fibronectin for all metal surfaces except for gold and titanium. [00125] The marked correlation between the surface energy measurements and the amount of protein bound on the surface indicates a relationship between protein binding and the magnitude of hydrophobic surface forces.

Electrostatic Force Testing [00126] Flat lxl cm square pieces (0.159 cm thick) of electropolished 316L stainless steel, nitinol with two different surface preparations: electropolished and electropolished/heat-treated, gold, tantalum and titanium were used for determination of relative metal surface electrostatic forces. All sample pieces underwent a standardized 5 step ultrasonic cleaning process as follows: initial bath in detergent (20% Extran 1000, VWR Science, West Chester, P.C.) followed by distilled water rinse, methanol rinse, acetone rinse and distilled water rinse, in sequence. After cleaning, the metal samples were placed in the AFM for acquisition of electrostatic force curves under dilute saline solution (pH 7.0). Ten electrostatic force curves were performed at each of 5 sites on each metal sample. A total of five samples of each different metal were measured.

[00127] Possible electrostatic heterogeneity was examined by obtaining force volume arrays. Force volume arrays were obtained by scanning a defined area of each surface by taking 32 curves per line, with 32 lines per area being scanned. A relative height by color was assigned to the electrostatic force level for each measurement taken. The result was a mosaic which depicts both the overall level of electrostatic force as well as a map of the surface charge variability within a given area.

Results of Electrostatic Force Testing

[00128] Examination of the color level of the force volume images, it was noted that the color for the volume images for gold and stainless steel are relatively homogeneous compared to the image for Nitinol. Additionally, gold and stainless steel appear to have similar electrostatic force levels that on average would be higher than the level obtained for the Nitinol image after averaging in the darker, or lower, measurements depicted. Figure 5 is a graph which depicts quantitative measurements taken on the metal samples, while Figure 6a graphically reflects the force volume images and Figure 6b are the individual force curves for each image.

[00129] Since the AFM used a negatively charged silicon nitride tip, as the tip is brought close to a negatively charged surface, double layer forces cause the tip to bend away from the surface and depart from a linear patter of descent to the surface. It is that departure that is measured as repulsive force, depicted by the shaded areas in Figure 6a. On the other hand, where the surface exhibits a positive charge relative to the tip, an attractive force is present which causes the tip to bend toward the surface and, also, depart from a linear descent to the surface. Thus, the force volume images indicate that both stainless steel and gold exhibit net repulsive forces whereas the curve for Nitinol exhibits a slight attractive force for the pixel selected. The cross-hair on the Nitinol curve represents a dark pixel on the force volume curve. Selection of a light colored pixel in the force volume image would have yielded a repulsive curve, demonstrating the heterogeneity of the electropolished Nitinol surface. [00130] Additionally, the difference in the intensity of surface-associated force between electropolished Nitinol and either gold or stainless steel is further substantiated by examining the relative z-position or distance from the surface that the silicon nitride tip first starts to bend and deflect away from the surface. In the case of gold and stainless steel, repulsive forces extend out to approximately 70 nm from the surface, but are only detected at 17 nm from the Nitinol surface.

[00131] Oxidation of the Nitinol surface, obtained by heat treating the Nitinol, yielded a more homogeneous force volume image than the electropolished Nitinol, and was similar to that observed with stainless steels, gold and titanium. Similarly, the distance from the oxidized surface at which force was detected increased to 90 mn from the 17 nm measured for the electropolished surface.

[00132] In comparing the results of total surface energy testing with electrostatic charge testing, there does not appear to be a direct correlation between surface energy and electrostatic charge. However, when total surface energy is compartmentalized into polar and nonpolar components, the polar component of surface energy exhibits a significant correlation to electrostatic surface forces. This correlation suggests that both surface energy and homogeneity of surface electrostatic charge are significant to protein adsorption and endothelialization.

[00133] These foregoing findings have direct applicability to implantable endoluminal device manufacture. In accordance with an aspect of the present invention there is provided an implantable endoluminal graft that is fabricated of a material having surfaces characterized by having controlled heterogeneities at the blood contact surface of the graft. Current manufacturing methods for fabricating endoluminal stents and grafts fail to achieve the desired material properties of the present invention. Presently, stents are made by machining a series of slots or patterns to accommodate radial expansion into a stainless steel or nickel-titanium metal hypotube, or by weaving wires into a self-expanding matrix. According to the present invention, an implantable endoluminal graft having controlled heterogeneities on at least one surface thereof is provided by fabricating the entire or individual components of the inventive endoluminal graft, including the structural support and the thin film covering by vacuum deposition techniques in which the process parameters of deposition are controlled to control the surface heterogeneities in the inventive endoluminal graft. Suitable deposition methodologies, as are known in the microelectronic fabrication arts and incorporated herein by reference, are plasma vapor deposition, chemical vapor deposition, physical vapor deposition and ion implantation which are utilized to impart a metal layer onto the stent and/or graft pattern which has a high amorphous content.

[00134] Figures 1-4 in the accompanying drawings illustrate one preferred embodiment of the present invention, while Figures 5-41 illustrate alternative embodiments of the present invention. Figures 42-43, 52 and 55-56 relate to the method of the present invention, while Figures 44-51 and 53-54 represent material characterization of the nitinol film and inventive grafts of the present invention fabricated by the inventive method.

[00135] Figures 1 and 2 show an implantable endoluminal graft 1 comprised of the structural support member 2 providing scaffolding for the microporous metal thin film covering 3. Figure 1 shows the implantable endoluminal graft 1 in its delivery profile or unexpanded state. Figure 2 shows the same implantable endoluminal graft 1 as it adopts its expanded state. In the expanded state, one can observe the cylindrical elements 4 and the interconnecting members 5 that form the structural support element 2. The microporous metal thin film covering 3 is attached to the structural support element 2 by attachment at a point on the terminal end 7 of a terminal interconnecting member 6. The terminal interconnecting member 6 may be at one or both ends of the structural support member 2, i.e., the proximal and/or distal ends of the implantable endoluminal graft 1; thereby allowing for attachment of the microporous metal thin film covering 3 at one or both ends thereof. Preferably, as shown in Figure 2, the interconnecting member 6 is present on the distal end of the structural support element 2; thereby allowing for attachment of the microporous metal thin film covering 3 only on the distal end of the implantable endoluminal graft 1. The interconnecting members 5 connect adjacent cylindrical elements 4 to one another in a manner that maintains the cylindrical elements 4 in-phase with one another. In order to maintain an in-phase relationship between adjacent cylindrical elements 4, the interconnecting members 5 connect a cylindrical element 4 at either a peak 8 or a valley 9 and connect to the corresponding peak 8 or valley 9 on an adjacent cylindrical element 4.

[00136] Attachment of the microporous metal thin film covering 3 to the structural support element 2 at the terminal end 7 may be achieved by chemical, mechanical or thermal means. For example, the attachment can be achieved by welding, adhering using a biocompatible adhesive, or by forming interlocking mechanical members on opposing surfaces of the microporous metal thin film covering 3 and the structural support element 2. Preferably, attachment is accomplished by forming a spot weld at the terminal ends 7. [00137] Figure 3 shows a structural support element 2 of an alternative preferred embodiment. This figure shows a structural support element 2 that is formed from cylindrical elements 4 attached to adjacent cylindrical elements 4 by interconnecting members 5. The interconnecting members 5 connect adjacent cylindrical elements 4 to one another in a manner that maintains the cylindrical elements 4 in-phase with one another. In order to maintain an in-phase relationship between adjacent cylindrical elements 4, the interconnecting members 5 connect a cylindrical element 4 at either a peak 8 or a valley 9 and connect to the corresponding peak 8 or valley 9 on an adjacent cylindrical element 4. The apices, which are the peaks 8 and valleys 9 of the cylindrical elements 4, are either attached to or not attached to interconnecting members 5. Opposing ends of each interconnecting member 5 are connected to adjacent cylindrical elements 4 at apices 12 and 15. The attachment between interconnecting members 5 and the adjacent cylindrical elements 4 forms a generally Y-shaped apex 20 and at an opposing end of the interconnecting member 5 forms a generally W-shaped apex 14. Finally, a generally U-shaped apex 14 is positioned without any interconnection member 5 and forms the intermediate apices between adjacent W-shaped apices 15. [00138] As illustrated in Figures 3 and 3A, and in accordance with a preferred embodiment of the present invention, it is advantageous to have a narrowed region 11 of each interconnecting member 5 at the junction position between the interconnecting member and the apex of the cylindrical member 4. Additionally, it is preferably that each apex 12, 14 and 15 of each cylindrical member 4 also be narrowed relative to the remaining section of the cylindrical member 4. In this manner, the width 2a of the material in the X-Y plane of the material at the apex is narrower than the width 2b of the material in the same X-Y plane of the remaining section of the structural support element 2. The narrowed region 11 and the narrowed region 2a of the apices are positioned in regions that are subjected to relatively higher strain during expansion of the structural support element 2 from its delivery diameter to its implanted diameter during endoluminal delivery and assist in relieving strain in these regions of the structural support element 2.

[00139] Additionally, the structural support element 2 can include additional features that can adjust its physical characteristics including longitudinal flexibility, radial expansion and hoop strength. The structural support element 2 can include reduced widths at the apices 8, 9, in both the cylindrical elements 4 and interconnecting members 5. This reduced width occurs in areas of increased stress, especially during radial expansion. During radial expansion, these high stress regions can experience cracks if the width is too large. Therefore, the width should be such that the high stress regions are able to meet the material strain, radial strength and expansible requirements of the structural support element. Additional flexibility of the structural support element can be provided by adding the generally U-shaped loop structures at the apices of the cylindrical elements. The generally U-shaped loop structures aid in unloading applied strain during radial expansion, thereby reducing the amount of stress transmitted to the remaining sections or struts of the cylindrical elements.

[00140] Alternative geometries are contemplated for the structural support elements 2. Such alternative geometries may include, for example, planar geometries for use as patches, frustroconical geometries such as for use as anchors for dental implants or other complex geometries such as for osteal implants. [00141] Figure 4 illustrates a fragmentary view of a segment of the structural support element 2 at an apex 15 of Figure 3 covered by the inventive microporous metal thin film covering 3. The microporous metal thin film covering 3 consists generally of a thin film metal covering material 17 having a plurality of micro-openings 19. The plurality of openings 19 preferably has an open surface area within the range of 0.5μm to 150μm, with the total open surface area being between 0.001 to 90%. The openings 19 permit cellular and sub-cellular physiological matter, such as proteins, to pass through the openings 19. Both the size of the openings 19 and the total open area of the microporous metal thin film covering 17 may be selected in view of the following non-exclusive factors: the desired flexibility of the graft, the desired hoop strength of the graft, the desired degree of geometric enlargement due to deformation of the openings 19 and the desired delivery profile size. The plurality of openings 19 impart dimensional flexibility to the microporous metal thin film covering 17, compressibility and expandability along the longitudinal axis of the implantable endoluminal graft 1, while also permitting compliance, foldabilty and expandability in the radial axis of the implantable endoluminal graft 1. The plurality of openings 19 are preferably provided in a pattern array in order to maximize the physical properties of the microporous metal thin film covering 17 and, hence, the resulting inventive implantable endoluminal graft 1. For example, the pattern array may be provided to selectively enhance longitudinal flexibility while reinforcing against radial compliance.

[00142] Alternative embodiments of the present invention can have a varying size of each of the plurality of openings in the microporous metal thin film covering so that cellular migration occurs through each opening, without permitting fluid flow there through. In this manner, for example, blood cannot flow through the plurality of openings (in the deformed or un-deformed state), but various cells or proteins may freely pass through the plurality of openings to promote graft healing in vivo. For some applications, moderate amounts of fluid flow through the plurality of deformed or un-deformed microperforations may be acceptable. For example, endoluminal saphenous vein grafts may be fabricated with openings in the microporous metal thin film covering that serve the dual function of permitting transmural endothelialization while also excluding biological debris, such as thrombus from passing through the wall thickness of the graft, effectively excluding detrimental matter from entering the circulation. In this example, each of the plurality of openings, in either their deformed or undeformed state, may exceed several hundred microns. [00143] Those skilled in the art will understand that a direct relationship exists between the size of pores and the overall ratio of expansion or deformability of an implantable graft. Generally, therefore, it is appreciated that pore sizes must increase in order to increase the effective attainable degree of expansion or deformation of the graft. Further descriptions of microporous metal thin film covering structures and, in particular, opening sizes are described in U.S. Patent Applications: Serial Nos. 10/135,316 and 10/135,626, which are hereby incorporated by reference. [00144] A structural support element 2 of an alternative preferred embodiment is illustrated in Figure 5. The interconnecting members 5 connect adjacent cylindrical elements 4 to one another in a manner that maintains the cylindrical elements 4 in-phase with one another. In order to maintain an in-phase relationship between adjacent cylindrical elements 4, the interconnecting members 5 connect adjacent cylindrical elements 4 at either a peak 8 or a valley 9 of a first cylindrical element 4 and connect to the corresponding peak 8 or valley 9 on a second cylindrical element 4. This pattern of connection forms either a peak- to-peak or a valley-to-valley interconnection. In addition to the terminal end 7 of the terminal interconnecting member 6, the structural support element 2 also has attachment members 50 attached to apices of cylindrical elements 4 other than the terminal cylindrical elements 4. The attachment members 21 resemble the terminal interconnecting member 6 but are located internally and attach to the microporous metal thin film covering 17 as illustrated in Figure 4. By providing additional attachment points, this preferred embodiment of the implantable endoluminal graft 1 allows for closer interaction and higher degree of correspondence between the structural support element 2 and the microporous metal thin film covering 17. The greater degree of correspondence results in less slippage or folding of the microporous metal thin film covering 17 relative to the structural support element 2.

[00145] Figure 6 illustrates a pattern of a plurality of openings 19 for a microporous metal thin film covering 17 in accordance with a preferred embodiment of the invention. Each of the plurality of openings 19 consists generally of a narrow longitudinal slot 23 having generally circular fillet openings 25 at opposing ends of each narrow longitudinal slot 23. It has been found preferable to provide the generally circular fillet openings 25 to enhance the ability of each of the narrow longitudinal slots 23 to widen and expand upon application of an expansive force perpendicular to the longitudinal axis of the microporous metal thin film covering 17 and of the narrow longitudinal slot 23. As depicted in Figure 6, each narrow longitudinal slot 23 is in its closed state as would be the case in the unexpanded state of the microporous metal thin film covering 17 of the present invention. In accordance with this embodiment of the invention, each of the openings 19 have a longitudinal axis that is parallel to the longitudinal axis of the microporous metal thin film covering 17. The openings 19 are in a staggered formation, so that adjacent openings 19 are positioned with an offset that is approximately one-half the length of an adjacent opening 19. This staggered pattern of openings 19, together with both the size and shape of the openings 19, provides a predetermined ratio of expansion along with both radial compliance and longitudinal flexibility for the microporous metal thin film covering 17. The thickness of the microporous metal thin film covering 17 may be between about 0.1 μm to about 20 μm, with a preferred range being between about 1 μm to about 10 μm, and a most preferred thickness being between about lμm and about 4.5 μm.

[00146] The high degree of flexibility of the microporous metal thin film covering 17 is illustrated Figure 7, which illustrates a segment of the microporous metal thin film covering 17 bent to traverse about 45 degrees. This configuration is contemplated to occur in curved regions of a body lumen, e.g., a curved portion of the vascular system. The implantable endoluminal graft undergoes curved configurations as it passes through a body lumen, which is not generally in a straight configuration; therefore, flexibility in the implantable endoluminal graft is important to traverse these regions without causing an impairment or injury to the lumenal system. In the curved configuration, the microporous metal thin film covering 3 is observed to have a compressed side 71 and an opposite, expanded side 72. Upon traversing the surface of the microporous metal thin film covering 3 perpendicular to the central axis of the implantable endoluminal graft 1, from the expanded side 72 to the compressed side 71, the openings 31 are observed to go from an about fully expanded opening 63 to a compressed opening 73, which undertakes a more elliptical form. A significant aspect of the present invention is that the plurality of openings 19 are capable of both expansion and contraction in response to either tensile forces or compressive forces exerted on the microporous metal thin film covering 3 and provide a high degree of compliance to resist buckling and wrinkling of the covering 3 surface as is typically found with conventional stent coverings.

[00147] Figure 8 illustrates a microporous metal thin film covering 3 of an alternative embodiment having two closed sections 80 surrounding an open section 81. In each closed section 80, the openings are closed openings 82, which are in a closed, unexpanded state. In the open section 81, each of the openings 83 have been subjected to a longitudinally expansive force and have changed from a slot shaped opening like each of the closed openings 82 and have opened to a diamond-like shaped opening characteristic of being under tension. Each of the closed openings 82 are oriented parallel to the longitudinal axis of the microporous thin film covering 3 and, therefore, under a longitudinally oriented tensile load will not open. In contrast, each of the openings 83 have their longitudinal axis oriented perpendicular to the longitudinal axis of the microporous thin film covering 3 and a longitudinally oriented tensile load will open each of the openings 83.

[00148] Figures 9-26 illustrate alternate patterns of the microporous openings that may be used in the inventive microporous metal thin film covering 3 in accordance with alternate embodiments of the present invention. Each opening pattern has its own unique physical characteristics, including porosity, diffusion rate therethrough, radial and longitudinal compliance, longitudinal flexibility, ratio of both radial and longitudinal expansion relative to the unexpanded state, and surface flow rates (i.e., the rate of flow across the surface). A given opening pattern may be selected based upon criteria established for the particular situation requiring intervention, e.g., for saphenous vein grafting, coronary artery stenting, aortic aneurysm exclusion, etc.

[00149] In Figure 9, opening pattern 90 is illustrated in which each of the plurality of openings 92 are generally longitudinal slots with generally circular fillet openings 94 at opposing ends thereof. The longitudinal axis of each of the plurality of openings is perpendicular to the longitudinal axis of the microporous metal thin film covering such that longitudinal expansive properties are imparted to the metal thin film covering. Adjacent rows of the longitudinal slots 92 are staggered on approximately one-half length spacing. [00150] Opening pattern 100 illustrated in Figure 10 is identical to that depicted in Figure 9, except that the longitudinal axis of the plurality of openings 102 is angularly displaced from the longitudinal axis of the microporous metal thin film covering, but is neither parallel nor perpendicular thereto.

[00151] Opening pattern 110 illustrated in Figure 11 is identical to that depicted in Figures 9 and 10, except that each of the plurality of openings 112 having filleted openings 114 have a longitudinal axis oriented parallel to the longitudinal axis of the microporous metal thin film covering such that radially expansive properties are imparted to the metal thin film covering.

[00152] In Figures 12 and 13, opening patterns 120 and 130 are similar to that depicted in Figure 9, except that the dimension of each of the longitudinal slots 122, 132 having filleted openings 124, 134 at opposing ends thereof have a longer dimension in the longitudinal axis of the opening 122, 132. In Figure 12, the longitudinal axis of the longitudinal slots 122 are perpendicular to the longitudinal axis of the microporous metal thin film to impart longitudinally expansive properties to the metal thin film covering, while in Figure 13, the longitudinal axis of the longitudinal slots 132 are parallel to the longitudinal axis of the metal thin film covering to impart radially expansive properties to the metal thin film covering.

[00153] The opening pattern 140 depicted in Figure 13 is similar to that depicted in Figure 9, except that there are a plurality of different length dimensions of the longitudinal slots 142 and 146, each having filleted openings 144 at opposing ends thereof and oriented perpendicular to the longitudinal axis of the microporous metal thin film covering.

[00154] Figure 15 illustrates yet another alternative opening pattern 150 in which there are a plurality of different length dimensions of the longitudinal slots 152, 156, 158, all having filleted openings 154 at ends thereof. Additionally, the opening pattern 150 is characterized by having groups of longitudinal slots 152, 156, 158 arrayed parallel to the longitudinal axis of the metal thin film covering and groups of longitudinal slots 152, 156 and 158 arrayed perpendicular to the longitudinal axis of the metal thin film covering such that a first group 150a and 150c have a common longitudinal axis, while second group 150b and fourth group 150d have a common longitudinal axis that is also perpendicular to the longitudinal axis of the first 150a and third 150c groups. Within each group adjacent rows of longitudinal slot openings are staggered on one-half length offsets. . In this manner, the microporous metal thin film covering has a generally checkerboard pattern of opening groups and will exhibit both radial and longitudinal expansibility.. [00155] Figure 16 is similar to Figure 15, except that there is a common longitudinal dimension of each longitudinal slot 162, again having filleted openings 164 at opposing ends thereof. Like the pattern 150 illustrated in Figure 15, opening pattern 160 is characterized by having groups of longitudinal slots 162 arrayed parallel to the longitudinal axis of the metal thin film covering and groups of longitudinal slots 162 arrayed perpendicular to the longitudinal axis of the metal thin film covering such that a first group 160a and 160c have a common longitudinal axis, while second group 160b and fourth group 160d have a common longitudinal axis that is also perpendicular to the longitudinal axis of the first 160a and third 160c groups. In this manner, the microporous metal thin film covering has a generally checkerboard pattern of opening groups and will exhibit both radial and longitudinal expansibility.

[00156] Figure 17 illustrates still another alternate geometry 170 of the microporous openings 172 in the metal thin film covering member 174. In accordance with geometry 170, each of the microporous openings 172 has a generally tri-leafed, Y-shaped opening with having each of the tri-leafs offset by approximately 120 degrees on center. The plurality of microporous openings 172 are arrayed in such a manner as to minimize spacing between openings 172 and have the metal thin film covering member 174 traverse a highly circuitous path between the plurality of microporous openings 172. This tri-leafed, Y- shaped opening shape of the microporous openings 172 will lend both radial and longitudinal expansion characteristics to the metal thin film covering member 172, and unlike the longitudinal slot openings of other embodiments previously described, also permits expansion along an axis intermediate to the radial and longitudinal axis of the metal thin film covering member 174. Upon expansion, each of the tri-leafed, Y-shaped openings expand to generally circular opening shapes. Figure 25 depicts a plan view of a graft material 260 having a plurality of tri-leafed Y-shaped openings 262 that is similar to the geometry 170, but in a larger view.

[00157] Figure 18 depicts another alternate geometry 180 for the inventive microporous metal thin film covering. In accordance with geometry 180, the plurality of microporous openings have several different opening shapes. A first opening comprises a plurality of elongate slot openings 182 having an enlarged intermediate section 181 and filleted openings 183 at opposing ends of each elongate slot opening 182. The elongate slot openings 182 are arrayed such that their longitudinal axis is parallel to the longitudinal axis of the metal thin film covering member. A second opening comprises a slot opening 184 having a longitudinal axis shorter than the first opening 182, has a uniform dimensioned intermediate section and filleted openings 183 at opposing ends thereof. Each of the second openings 184 has a longitudinal axis perpendicular to the longitudinal axis of the metal thin film covering member. Finally, a third opening 185 is provided with an enlarged generally S- shape, with its longitudinal axis arrayed generally parallel to the longitudinal axis of the metal thin film covering member. In accordance with geometry 180, the plurality of first openings 182 are arrayed in adjacent offset rows along the longitudinal axis of the metal thin film covering member. A second opening 184 is positioned between pairs of longitudinally adjacent first openings 182 and positioned to form circumferentially oriented rows perpendicular to the longitudinal axis of the metal thin film covering member. The plurality of third openings 185 are positioned in longitudinally expending rows intermediate circumferentially adjacent longitudinal rows of the first opening 182 and between adjacent circumferential rows of second opening 184.

[00158] In accordance with another preferred embodiment, geometry 190 is provided. In accordance with geometry 190, a plurality of tri-legged, generally Y-shaped openings 190 are provided in the metal thin film covering material 194, with the openings 190 being oriented in an offset array along either the longitudinal or circumferential axis of the metal thin film covering material 194. Like the embodiment illustrated in Figure 17, openings 190 permit expansion of the metal thin film covering material 194 along virtually any axis of the material 194, thereby imparting a high degree of compliance. Upon expansion, each of the openings 190 will assume a generally circular shape. Figure 26 depicts a plan view of a graft material 270 having a plurality of tri-leafed Y-shaped openings 272 that is similar to the geometry 190, but in a larger view.

[00159] Figure 20 illustrates still another embodiment of a pattern 200 of microporous openings. Like geometry 190, there are provided a plurality of tri-leafed, Y- shaped openings 202 arrayed along both the longitudinal circumferential axes of the metal thin film covering material 208. However, in pattern 200, each of the tri-leafed legs of the openings 202 have generally circular fillets 204 at ends thereof and a pair of generally triangular shaped openings 206 on opposing lateral aspects of each of the tri-leafed legs. Like geometry 190, pattern 200 will exhibit compliance in virtually any axis of the metal thin film covering material 208.

[00160] Figures 21 and 22 represent alternate related geometries 210 and 220, respectively. Common to both geometries 210 and 220 are a plurality of elongate longitudinally extending slots 212, 222 having generally circular fillets 214, 224 at opposing ends thereof, and arrayed in adjacent, offset rows extending along the longitudinal axis of the metal thin film covering member. A plurality of relative shorter circumferentially oriented slots 216, 226, also having generally circular fillets at opposing ends thereof, are arrayed adjacent, offset rows extending along the circumferential axis of the metal thin film covering member. Each of the plurality of relatively shorter slots 216, 226 is positioned intermediate longitudinally adjacent pairs of elongate longitudinally extending slots 212 and 222. The difference between geometry 210 and 220 is that in geometry 220 there are an additional plurality of generally trapezoidal fenestrations 225 in the metal thin film covering material 228 that are bounded by section of two circumferentially adjacent and offset elongate slots 222 and two longitudinally adjacent and offset relatively shorter slots 226. Both geometries 210 and 220 will lend compliance in both the radial and the longitudinal axis of the metal thin film material.

[00161] Figure 23 illustrates yet another geometry 240 for the openings in the metal thin film covering material 248. Geometry 240 displays a high degree of similarity to geometry 180 illustrated in Figure 18, except that all of the longitudinal slot openings 242 have an enlarged intermediate section 241, and are arrayed in both the longitudinal axis and the circumferential axis of the metal thin film covering material 248, such that a single circumferentially oriented slot opening 242 is positioned intermediate adjacent pairs of longitudinally oriented slot openings 242. A plurality of generally cruciform fenestrations 246 are also provided in the metal thin film covering material 248 and are bounded by a pair of longitudinally oriented slot openings 242 and a pair of circumferentially oriented slot openings 242. Geometry 240 will exhibit compliance in both the longitudinal and circumferential axes of the metal thin film material 248.

[00162] Finally, Figure 24 depicts another geometry 250 of the openings in a metal thin film material. Geometry 250 includes a plurality of circumferentially oriented elongate slots 252 and a plurality of longitudinally oriented elongate slots 254 oriented generally perpendicular with respect to one another. A plurality of generally circular openings 256 pass through the metal thin film material 258 in an area bounded by a pair of circumferentially extending elongate slots 252 and a pair of circumferentially extending elongate slots 254. Geometry 250 will also exhibit compliance in both the longitudinal and circumferential axes of the metal thin film material 258.

[00163] Figures 27-40 illustrate different geometries of structural support elements 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 420, 430, 440, and 450 of alternative embodiments of the present invention. The various structural support elements exhibit the ability to radially expand and support a microporous metal thin film covering and also have the flexibility to maneuver through anatomic passageways including the vascular system. In addition to the depicted geometries, other known geometries of stents are contemplated for alternative embodiments of the present invention provided that the stent geometry has the necessary ability to radially expand and support a microporous metal thin film covering and the required flexibility. [00164] Figure 27 depicts an embodiment of structural support element 300 in which the there are provided a plurality of linear longitudinal elements 304a-304e, and a plurality of undulating circumferential elements 306a-306e, where each of the plurality of linear longitudinal elements 304a-304e form four point connections 305 with circumferential elements except for an end terminal circumferential element 304e which form three point connections 305. Notably, at least some of the linear longitudinal elements 304a-304e further have a terminal extension 309 that projects outward from at least one terminal end of the structural support element 300 and has a filleted rounded end 309a that serves as an attachment point for a metal thin film material (not shown). In accordance with a preferred embodiment, each of the undulating circumferential elements 306a-306e have a generally sinusoidal shape with a plurality of interconnected peaks 303 and valleys 301.

[00165] As illustrated in Figures 28A and 28B, the linear longitudinal interconnecting elements 311 and 312 between adjacent pairs of circumferential elements, may have different lengths which either decreases, in the case of shorter length longitudinal interconnecting elements 311, or increases, in the case of longer longitudinal interconnecting elements 312, the spacing between adjacent pairs of circumferential elements and alters the longitudinal flexibility of the structural support member.

[00166] Figures 29-33 illustrate alternate embodiments in which the undulating circumferential elements 306 are interconnected by different configurations of interconnecting elements 304, such as non-linear interconnecting elements 304 that have alternate spacing and either connect peak-to-peak or peak-to-valley of the adjacent pairs of undulating circumferential elements 306.

[00167] Figures 34-40 illustrate alternate embodiments 380, 390, 400, 420,

430, 440, 450 of the structural support member in which the circumferential elements 306 have apices at the peaks and the valleys that have a generally semicircular or C-shape, and each of the interconnecting elements 304 are non-linear bent elements having a generally U- shaped apex intermediate its length. The principal difference between the illustrated alternate embodiments lies in the number and spacing of the interconnecting elements 304.

[00168] Figure 41 illustrates an expanded view of a particular geometry of a structural support element with portions of microporous metal thin film coverings 3 shown within the interstices 410. Four different microporous metal thin film coverings 3 are shown that have different opening patterns 200, 90, 240 and 270 as previously described, it being understood that it is preferable in accordance with the preferred embodiment that a single type of opening pattern in the microporous metal thin film material 3 be employed across the entire structural support element. By covering the interstices 410, the microporous metal thin film coverings 3 create continuous microporous surface that limits passage of fine materials through the interstices 410 while acting as a tissue growth scaffold for eliciting a healing response. Based upon the aggregate open areas of the microporous metal thin film coverings 3, the rate of diffusion of cellular and sub-cellular species and fluids through the interstices is altered.

[00169] The microporous metal thin film covering 3 may be fabricated of preexisting conventionally produced wrought materials, such as stainless steel or nitinol hypotubes, or may be fabricated by thin film vacuum deposition techniques. In addition to wrought materials that are made of a single metal or metal alloy, the inventive grafts may be comprised of a monolayer of biocompatible material or of a plurality of layers of biocompatible materials formed upon one another into a self-supporting laminate structure. Laminate structures are generally known to increase the mechanical strength of sheet materials, such as wood or paper products. Laminates are used in the field of thin film fabrication also to increase the mechanical properties of the thin film, specifically hardness and toughness. Laminate metal foils have not been used or developed because the standard metal forming technologies, such as rolling and extrusion, for example, do not readily lend themselves to producing laminate structures. Vacuum deposition technologies can be developed to yield laminate metal structures with improved mechanical properties. In addition, laminate structures can be designed to provide special qualities by including layers that have special properties such as superelasticity, shape memory, radio-opacity, corrosion resistance etc.

[00170] According to the preferred method of making the inventive medical devices, including the structural support element and the thin film metal member, fabrication by physical vapor deposition of metallic and/or pseudometallic films is desirable. A preferred fabrication method of the present invention is described in the following. A precursor blank of a conventionally fabricated biocompatible metal or pseudometallic material, or alternatively, a precursor blank of a vacuum deposited metal or pseudometallic film is employed. Either precursor blank material is then preferably masked, leaving exposed only those regions that will define defining the plurality of openings 31 (see Figure 4). The exposed regions are then subjected to removal either by etching, such as by wet or dry chemical etching processing, with the etchant being selected based upon the material of the precursor blank, or by machining, such as by laser ablation or EDM. Alternatively, when employing vacuum deposition, a pattern mask corresponding to the plurality of openings may be interposed between the target and the source and the metal or pseudometal deposited through the pattern mask to form the patterned openings. Further, when employing vacuum deposition, plural film layers maybe deposited to form a laminate film structure of the film prior to or concurrently with forming the plurality of openings. [00171] Where a laminate film is fabricated as the graft, it is necessary to provide for good adhesion between the layers. This may be achieved by providing for a relatively broad interfacial region rather than for an abrupt interface. The width of the interface region may be defined as the range within which extensive thermodynamic parameters change. This range can depend on the interface area considered and it may mean the extent of interface microroughness. In other words, adhesion may be promoted by increased interfacial microroughness between adjacent layers within the film. The microroughness may be imparted by chemical or mechanical means, such as chemical etching or laser ablation, or may be included as a process step during vacuum deposition by selectively depositing a metal or pseudometallic species to form the microroughness. [00172] Thus, the present invention provides a new metallic and/or pseudometallic implantable graft that is biocompatible, geometrically changeable either by folding and unfolding or by application of a plastically deforming force, and capable of endoluminal delivery with a suitably small delivery profile. Suitable metal materials to fabricate the inventive membranes are chosen for their biocompatibility, mechanical properties, i.e., tensile strength, yield strength, and their ease of deposition include, without limitation, the following: titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, such as zirconium-titanium-tantalum alloys, nitinol, and stainless steel. Examples of pseudometallic materials potentially useful with the present invention include, for example, composite materials, ceramics, quartz, and borosilicate.

[00173] The present invention also provides a method of making the inventive implantable endoluminal graft devices by vacuum deposition of a graft-forming metal or pseudometal and formation of the openings either by removing sections of deposited material, such as by etching, EDM, ablation, or other similar methods, or by interposing a pattern mask, corresponding to the openings, between the target and the source during deposition processing. Alternatively, a pre-existing metal and/or pseudometallic film manufactured by conventional non-vacuum deposition methodologies, such as wrought hypotube, may be obtained, and the micro-openings formed in the pre-existing metal and/or pseudometallic film by removing sections of the film, such as by etching, EDM, ablation, or other similar methods. An advantage of employing laminated film structures to form the inventive graft is that differential functionalities may be imparted in the discrete layers. For example, a radiopaque material such as tantalum may form one layer of a structure while other layers are chosen to provide the graft with its desired mechanical and structural properties.

[00174] As an aid to understanding the present invention, Figure 43 provides a diagrammatic view of a vacuum sputter deposition system 50 useful in practicing the inventive methodology. In deposition system 50 there is provided an exterior housing 54, a cooling jacket 52 in thermal contact with the hollow cathode 60, a cylindrical target 64, a substrate 62 positioned along the central axis of the system 50, and a rotary motor 63 coupled to the substrate 62 for providing rotational motion to the substrate within the system 50. Seals 56 serve to isolate deposition chamber 58 from the ambient environment. A gas feed input port 68 permits the introduction of argon gas into the deposition chamber 58, while a vacuum port 66 permits communication between the deposition chamber 58 and vacuum pumps to obtain a vacuum within the deposition chamber 58. A scrubber 69 is preferably placed upstream to and in line with the gas feed input port 68 in order to provide purify the working gas of contaminants, particularly oxygen or nitrogen that may be present in the gas. [00175] It has been found that the resultant strength of a vacuum deposited nitinol material is dependent entirely upon the target composition and the process parameters employed during vacuum deposition. In accordance with the present invention, it has been found desirable to achieve a balance of a multiple number of process parameters, each of which influence the resulting mechanical and physical properties of the resulting nitinol material. [00176] In accordance with the best mode contemplated for the present invention, during deposition, the deposition parameters are controlled to optimize deposition of nitinol onto the substrate. Specific definition of the sputtering process includes the detailed geometry of the sputtering device including the magnetic field strength and distribution. In the case of hollow cathode dc sputter deposition, the sputtering parameters include but are not limited to the following: the base pressure of the vacuum system, the quality and pressure of the process gas, the quality and finish of the substrate material, the temperature of the substrate, the power and voltage supplied to the cathode, the material quality of the target or targets, the target surface temperature, and the throw distance. A judicious choice of these parameters enables one to produce high-strength vacuum deposited shape memory materials with the required microstructure and the proper chemical composition to control A_p, without the need for precipitation annealing.

[00177] The rate of film growth is another significant parameter of deposition processes. In order to deposit materials that are sufficiently thick so that they can be compared in functionality with wrought metal products, deposition rates in the order of 1 μm/hour or higher are desirable. Depending on other deposition parameters, and most importantly on the substrate temperature in vacuum deposition methods, the structure of the deposit may be amorphous or crystalline. When hollow cathode dc sputtering techniques are employed, a high strength 5 μm thick nitinol film may be deposited in about less than one hour.

[00178] In accordance with the method of the present invention, the inventive material is made by positioning a cylindrical deoxygenated copper mandrel along the axis of a cylindrical hollow cathode dc magnetron sputtering device. The sputtering target is formed from a nitinol sheet that has a thickness of about between 1 and 3 mm. The target is formed into a cylindrical shape so that it forms a continuous cylindrical surface. In accordance with a preferred embodiment of the invention, the target is made of nitinol sheet with either Ni or Ti added in form of spot welded wires to the working target surface. The transition temperature of the deposited film may be shifted to lower values by the addition of Ni wire, whereas the transition temperature may be shifted to higher values by the addition of Ti wire. Alternatively, the target maybe made of either a titanium or nickel sheet or tube and either nickel or titanium pieces, respectively, bound to the surface of the sheet or tube, such as by welding. Finally, minor alloying components, such as tantalum, may be added to the target by affixing wires or sheets of the alloying component to the target. The target is placed inside the cathode and electrical contact is made between the cathode body and the target. [00179] It is known and well accepted in the conventional methods of sputter deposition to maintain thermal contact between the cathode and target such that the cathode cooling jacket act to dissipate heat from both the target and the cathode, thereby cooling the target. Usually, the cathode is cooled using water circulation or sometimes using Peltier cooling elements. However, in a departure from these conventional methods of magnetron sputtering, and in accordance with one preferred embodiment of the present invention, the thermal contact between the cathode and the target is intentionally reduced. While cathode cooling is maintained in order to protect the magnets of the magnetron from overheating, the thermal contact between the cathode and the target is reduced or substantially eliminated. [00180] Thermal isolation of the target from the cathode is achieved by interposing a thermally insulating or dielectric material between the cathode and target. In one embodiment, this material may be a ceramic cylinder; in an alternative embodiment, it may be a set of thin thermally conductive spacers, such as metal, that reduce the heat conductivity between the cathode and target may be employed to reduce the cooling of the target and permit target heating, but to a lesser degree that where the target is thermally isolated from the cathode cooling jacket.

[00181] Alternatively, in accordance with another preferred embodiment of the invention, the target may be in full thermal contact with the cathode. In this embodiment the thermal contact between the target and the cathode is unchanged from conventional sputter deposition methodologies and no reduction in thermal coupling is employed. However, in order to adjust for the cooler target surface conditions, other sputter deposition process parameters are adjusted, such as the magnetic field strength, the working gas pressure, the target-substrate throw distance, the sputtering power and/or the cathode voltage are adjusted in order to maintain sufficient energy being applied to the target species to ensure adequate energies of the species arriving at the substrate surface.

[00182] It is known in the vacuum deposition arts that sputtering is best carried out in vacuum systems with the base pressure in the high vacuum range, i.e. about in the 10^"6- 10^"7 Torr range, or better. The working gas pressure during the deposition is typically between about 0.1 mTorr and 30 mTorr. While the working gas is preferably argon, alternative gases such as from He, Ne, Kr, or Xe may be employed. At a normal purity level of 99.999% for high purity Ar, the total partial pressure of the contaminants at less than about 30 mTorr working pressure is less than about 3x10^"7 Torr, which is typically considered acceptable for sputter deposition. [00183] In a departure from this conventional practice, in accordance with the best mode of the inventive process includes additional steps are employed to reduce the impurity levels of the working gas. In order to reduce the impurity level of the argon working gas, a scrubber is added to the argon gas line to reduce oxygen in the argon input feed line. The scrubber employs heated titanium that oxidizes to titanium oxide and captures contaminating oxygen in the argon feed line. Additionally, the in accordance with the best mode of the inventive method it is desirable to include a titanium sublimation pumping system to reduce the O₂ partial pressure in the working gas during the deposition. While the foregoing steps have been employed in accordance with the method of the present invention, those of ordinary skill in the vacuum deposition arts will understand that alternative methods for removing impurities in the gas feed and to reduce the oxygen background pressure may be employed.

[00184] As illustrated in Figure 42, the inventive method 10 generally comprises the steps of providing a deposition reactor having a vacuum system and dc magnetron 12, providing and preparing a target 14 and a substrate 16, loading the target and substrate into the reactor 18, then obtaining a vacuum in the reactor 20. Argon working gas is introduced into the reactor and a plasma is ignited 22, the target is conditioned 26 and the substrate preheated 24. It is preferable to condition or clean the surface of the nitinol target prior to deposition the first time by creating plasma within the chamber and exposing the target to the plasma for a period of several hours. After the first use and prior additional uses, the target is conditioned for a shorter period of time (for example, for 30 min), such that is sufficient for the plasma process to reach steady state. After the substrate is pre-heated and the target is prepared, the substrate is positioned within the dc magnetron 28, and the sputter deposition process is initiated 30 by applying a voltage to the cathode. It has been found that negative bias voltage of between about 40 V and 120 V, preferably between 60 V and 100 V, is desirable in order to impart additional energy to the Ni and Ti atoms that arrive onto the substrate and form the deposited film. This additional energy through a "peening" effect results in high film density and stronger films. Where there is a cylindrical substrate, it is desirable to rotate the substrate 32 during the deposition run. Film deposition is preferably carried out at a rate of between about 2 and 10 μm per hour. After the deposition run, the deposited film is cold quenched 34 within the vacuum system, then removed from the vacuum system 36. In accordance with the invention, post-deposition processing of the deposited film may be employed while the film remains on the substrate 38. For example, laser or chemical etching of the deposited film may be employed in order to impart a desired geometric pattern to the film, or dimension the film for its intended use. Finally, the deposited film is removed from the substrate 40.

[00185] The power input from the dc magnetron power supply in combination with the power input from the biasing power supply result in energy being dissipated in the target, the plasma and the substrate. In addition, the substrate may be heated by a separate heat source. Normally, the cathode cooling would serve as a heat sink to dissipate heat from the target and cathode. However, because in the inventive sputtering method the thermal contact between the target and the cooling is attenuated or eliminated, the applied energy heats the target, the working gas, and the substrate. The heating effect may be controlled by adjusting the power input, the level of thermal coupling between the target and cathode, and/or by adjusting the thermal conductivity of the substrate holder.

[00186] The significance of the substrate temperature is well understood in the deposition arts. On relatively cooler substrates films growth is essentially amorphous, with grain size increasing with the substrate temperature. At lower substrate temperatures there is an increased tendency for columnar film growth.

[00187] We have recognized, however, that higher deposition temperatures may not be as significant in reducing columnar growth, as is the level of energy of the sputtered atoms arriving at the substrate surface. Apart from their effects on the resulting deposited material, the sputtering process itself is largely independent of the target and gas temperature. The elevated target temperature has greater significance where multicomponent targets are employed. With multicomponent targets, preferential sputtering of an individual component combined with radiation enhanced segregation and diffusion can take place. With nitinol, however, at low temperatures where the components are "frozen" and immobile, after initial transients the sputtering yields of Ni and Ti even out.

[00188] However, perfect reproduction of the target composition is typically not achieved in the deposited film. It is thought that two reasons exist for this phenomenon. First, the Ni and Ti atoms have to reach the substrate after traveling through the distance separating the target from the substrate, called the throw distance. Second, the angular distribution of the sputtered Ni and Ti atoms is different. Ni tends to have a lower ejection angle relative to the surface of the target, while Ti has a greater ejection angle and leaves the target surface at a higher angle of incidence relative to the target surface. This difference in ejection angle between nickel and titanium, results in a lower Ti content and in lateral inhomogeneity of the nitinol films. [00189] In conventional planar sputtering equipment the throw distance is typically 2-6" or about 5 cm to 15cm. The significance of the throw distance is that the Ni and Ti atoms have a chance to collide with the atoms of the working gas, scatter, and be either re-deposited on the target or be entirely lost from the deposition process by being deposited elsewhere. The longer the throw distance, and the higher the gas density, the bigger are the re-deposition effects and the losses. The scattering cross section is larger for the Ti atoms than for the Ni atoms and hence the tendency, under usual circumstances, of depositing films with higher Ni content. This effect is counteracted to some extent by the fact that the re-deposited material is preferentially sputtered. Common solution to this problem is to add extra Ti in the form of additional targets or target pieces. However, such solutions may lead to laterally inhomogeneous deposits and loss of the fine composition control that is required for the deposition of useful nitinol films. The atom scattering between the target and substrate results in Ti deficiency and in temporal inconsistency of the deposited nitinol composition because of the combination of the transient effects involved. [00190] In contrast, at elevated temperatures the target surface composition is influenced by the segregation of Ti, i.e., there is an excess Ti concentration at the target surface. This leads to more Ti sputtered and Ti-enriched films produced. In addition, the target becomes slowly depleted in Ti. The control of the target temperature provides a fine control over the Ti content in the deposited nitinol. Depending on the desired transition temperature of the nitinol deposit, one can select the deposition power to optimize the target temperature for the required Ti segregation, and one may improve substrate cooling or introduce additional substrate heating in order to optimize the process.

[00191] The substrate temperature is preferably kept above 400 °C and, most preferably, is about 500 °C. At these temperatures interdiffusion between the deposited nitinol and the typically oxygen-free Cu (OFE Cu) substrate material is negligible, yet the surface mobility of the deposit is sufficiently high in order to help to suppress columnar growth. Vacuum deposition onto a substrate that is not pre-heated is also contemplated by the present invention. By controlling the other process parameters, it is possible to impart sufficient energy to particles arriving at the surface of the substrate to suppress columnar growth and the inventive high-strength nitinol material may be fabricated without the need for substrate pre-heating.

[00192] In accordance with the present invention, it has been found preferable to have a throw distance less than about 2.5 cm. By employing a smaller throw distance and minimized Ar pressure relative to the conventional deposition processing, scattering of the Ni and Ti atoms during deposition is limited and an atomic concentration of Ni to Ti closer to that of the target is more readily achieved.

[00193] In addition to the above considerations, the throw distance, the pressure and temperature have an additional significance heretofore not sufficiently recognized. Under typical deposition conditions (Ar pressures and temperatures) used in the sputtering arts, the mean free path is in the mm range during the deposition process. The sputtered atoms leave the target surface with a few eV energy (the most probable value within a quasi Maxwellian distribution with a long high energy tail). Due to the fact that the typical throw distance is several cm, i.e., about an order of magnitude longer than the mean free path, the sputtered atoms typically suffer several collisions before they are deposited. As a result, they lose much of their initial kinetic energy, or thermalize. However, this energy plays an essential role in providing for crystalline film growth without columns. The combination of the deposition parameters described in the exemplary deposition process ensures that the throw distance and the mean free path are of comparable magnitude. Other sets of parameters may be able to provide for the same result and thus may achieve the same nitinol film properties as described herein.

[00194] The cylindrical magnetron geometry is essentially the same as having a large planar target and a large parallel planar substrate. Large is defined here as having large dimensions compared to the target to substrate distance. The distance between the target and the substrate is uniform in both cases. Assuming a cosinusoidal distribution of the sputtered particles, the real throw distance, i.e., the average flight distance between two planes (target and substrate) is illustrated with reference to Figure 52. The geometric distance is ; a generic flight direction is at the angle φ, at this direction the distance is /. Then the average is calculated as

<img file="WO2004028340A2_D0001.tif" /> where

<img file="WO2004028340A2_D0002.tif" /> is the distribution function. The evaluation of the integral yields

&lt;/&gt;=4/ /τr = 1.27/₀. (3) [00195] The throw distance is somewhat higher for the Ti atoms than for the Ni atoms because, as experiments show, the Ni distribution is somewhat narrower than cosinusoidal (V.S. Chernysh, V.S. Tuboltsev, V.S. Kulikauskas "Angular distributions of Ni and Ti atoms sputtered from a NiTi alloy under He⁺ and Ar⁺ ion bombardment" Nuclear Instruments and Methods in Physics Research B, Vol. 140, 1998, pp. 303-310). [00196] The mean free path (MFP) can be taken to be inversely proportional to the colhsional cross section and hence proportional to the square root of the atomic mass: λ oc (4)

[00197] Since the average atomic mass of Ni is 58.71 g/mol and the average atomic mass of Ti is 47.90 g/mol, the ratio of the MFPs is 1.11. Assuming that the effect on the composition is a result from colhsional loss of Ti, the effect should be proportional to the average number of collisions on the way from the target to the substrate. This collision frequency can be estimated as the ratio of the throw distance and the MFP. It is difficult to accurately estimate the MFP but we can estimate it to be close to the Ar MFP and then modify it by the square root rule (4). At 10 mTorr the Ar MFP 1=4.9 mm. This is for 300K. At 800K (an estimated temperature of the working gas during deposition with a hot target), and taking into account that ions have MFPs 2 times of atoms, one obtains 1=18.5 mm. The collision frequency N can be estimated then as

N = — (5) λ

[00198] Then the effect on the composition can be estimated as

C Ni oc : l jM M_n f (6)

[00199] This formula can be used to show that a 3 mm change in the target- substrate distance from 20 mm to 17 mm can result in 0.6-0.7at% change in the Ti content and therefore in a 60-70 °C change in the transition temperature of the deposited film.

[00200] In accordance with the best mode known to the inventors, the inventive deposition process comprises generally the following steps: a. A nitinol target is prepared such that it fits into the HC magnetron but the thermal contact between the water-cooled cathode and the target is interrupted by placing a thin ceramic cylinder between the cathode and the target; b. Electrical contact is provided between the cathode and the target; c. The substrate is oxygen-free (OFE) copper tube polished on its outside to a surface finish where the surface roughness is Ra&lt;50 nm for a 500 μm long trace with a 100 μm low pass filter; d. The substrate is placed in the deposition chamber which is subsequently pumped to a base pressure about &lt;2xl0^"7Torr; e. The substrate is preheated to a temperature between about 400 °C-500 °C, alternatively, it is also contemplated that the substrate preheating step may be eliminated, and the deposition occur onto a non-preheated substrate surface; f. Pure Ar gas (99.99% or purer) is admitted to the deposition chamber at a pressure between about 1 mTorr and 20 mTorr; g. Target conditioning: The magnetron is powered up to produce plasma and is used for about 10-40 min with a dummy substrate to achieve stable deposition conditions. The magnetron power is about between 0.1 kW and 1 kW for a target size of about 50 mm diameter and about 150 mm length. The voltage on the cathode is maintained between about 400 V and 1000 V, preferably between 600 - 900 V, and is kept constant. The Ar gas feed is regulated to adjust the Ar gas pressure to maintain a constant cathode voltage; h. The substrate is moved in the sputtering position which provides for a throw distance of about 10 mm to 25 mm, which is about equal on all sides; i. The substrate is rotated along its longitudinal axis with a rotational velocity of about between 10 rpm and 200 rpm; j. A negative bias voltage between about -60 V and -100 V is provided to the substrate; k. The sputtering is carried out for a duration that provides the desired thickness of the deposit; and 1. After the deposition is complete, the plasma is turned off and the deposit is quenched in vacuum by admitting cold Ar (cooled using a coil immersed into an alcohol and dry ice mixture coolant) into the deposition chamber.

[00201] At this point, the material, still on the mandrel, is removed from the vacuum deposition chamber and the copper mandrel is chemically removed. Additional post- deposition steps of surface finishing, cutting, etc. may be employed.

[00202] The device may be removed from the substrate after device formation by any of a variety of methods. For example, the substrate may be removed by chemical means, such as etching or dissolution, by ablation, by machining or by ultrasonic energy. Alternatively, a sacrificial layer of a material, such as copper, or nickel, may be deposited intermediate the substrate and the nitinol tube or the device formed there from. The device maybe formed while the nitinol tube is still on the mandrel using laser cutting, laser ablation, or chemical or electrochemical etching with the use of a photolithographic pattern, or any similar methods. Then it maybe removed by melting of the sacrificial layer, selective chemical etching of the same, or using other suitable means.

[00203] The resulting device may then be subjected to post-deposition processing to modify the crystalline structure, such as by annealing, or to modify the surface topography and composition, such as by cleaning and passivation.

[00204] Figure 44 is electron microprobe spectrum of the inventive nitinol film deposited by sputter deposition in accordance with the method of the present invention. The spectrum was obtained on the outside surface of a 6.35 mm sputter deposited nitinol tube. Measurement was taken using energy dispersive spectroscopy (EDS). The data demonstrates that the film is a pure, stoichiometric nitinol. The presence of trace amounts of aluminum and silicon is attributed to surface contamination. X-ray diffraction analysis of the same material confirmed 100% crystallinity of the nitinol film.

[00205] Figure 45 is a graph illustrating testing by differential scanning calorimetry (DSC) of the inventive film produced by the inventive method. The DSC curve demonstrates a robust transition exhibiting a high ΔH value of 24.4 J/g. The results of testing the inventive high-strength nitinol film using dynamic mechanical analysis (DMA) are set forth in Figure 46. Figure 46 is the stress-strain curves for the inventive nitinol thin film, Curve A, and a wrought nitinol sheet, Curve B. The wrought nitinol sheet was thinned by chemical etching to achieve a thickness of about 10 μm suitable for testing on the DMA instrument. The inventive nitinol film A broke at the highest stress and strain depicted on the graph, thus, the ultimate stress was approximately 1250 MPa, while the ultimate strain was about 12%. The results shown in Figs. 4 and 5 were obtained on the same film. The wrought nitinol film did not break, but testing reached the load limit of the DMA instrument at approximately 1400 MPa and a strain limit of about 7.5%.

[00206] Figures 47A and 47B are a scanning electron micrographs of a prior art sputter deposited nitinol film (a transverse cross-section of a 5μm thick sample of the inventive nitinol film taken at 10,000X magnification. The Figure 47A illustrates the microstructure morphology of conventionally sputter deposited nitinol film (Chu, J.P., et al. Deposition and characterization ofTiNi-base thin films by sputtering, Materials Science and Engineering. A 277 (1-2) (2000) pp. 11-17) which is characterized by having a generally columnar texture of the film. Figure 47B is a fractured transverse cross-sectional scanning electron micrograph of a section of an inventive 5μm film. It is readily apparent that the inventive film exhibits a complete absence of columnar morphology and is characterized by a grain structure which exhibits close compaction and virtually no surface roughness. [00207] Figure 48 is an x-ray diffraction graph of a 5μm sample of the inventive nitinol material. The strong peak of approximately 3600 cps intensity at about 438 on the 2Θ axis, without the presence of any other significant peaks is clearly indicative of the absence of precipitates in the inventive nitinol material. [00208] Figure 49 is a transmission electron micrograph taken on the same 5μm sample of inventive nitinol material used for the x-ray diffraction depicted in Figure 7. The micrograph verifies that the average grain size for the inventive nitinol material is about 0.1 μ. [00209] Figure 50 is an electron diffractogram taken on the same 5μm sample of inventive nitinol as depicted in Figures 7 and 8, and depicts a virtually complete absence of precipitates. There is a very faint trace of a Ti₃Ni₄ present, however, there is no evidence of other precipitates in the diffractogram. [00210] Figure 51 is a surface scan using surface profilometry taken on the luminal surface of an inventive nitinol material formed as a cylindrical tube. The low surface roughness of the deposited material is the result of the smoothness of the substrate and is determined by the nature and extent of pre-deposition substrate polishing and surface preparation. [00211] Figure 53, panels a and b, and Figure 54 are optical micrographs in dark field (Figure 53, panels a and b) and bright field (Figure 54) microscopy illustrating a more gross view of the outside surface of the inventive material. In Figure 53, panel a, is shown a surface of a 5μm nitinol film having substantial surface roughness which is obtained where energetic particles are excluded from the substrate. Such a surface is characteristic of a columnar morphology depicted in Figure 47A. In distinction to Figure 53, panel a, panel b illustrates a substantially smoother outside surface where energetic particles are permitted to reach the substrate. Thus, the smoother surface profile shown in Figure 53, panel b, which is consistent with the inventive nitinol material, represents a more perfect nitinol material than that obtained using the conventional sputter deposition process methodology depicted in Figures 47A and panel a of Figure 53.

[00212] Gross characterization of the resulting post-deposition film may be performed to determine whether the nitinol film grew with a columnar grain structure or with a non-columnar grain structure. As illustrated in Figure 54, there is a difference in the luster between films and fill regions having columnar texture and films with non-columnar grain morphology. When nitinol is grown with a columnar texture, the columns are typically 0.1-1 micron in diameter, which yields a resulting surface that is rough and scatters ambient light, resulting in a reduced surface luster. Where, however, the nitinol film has a non-columnar grain structure, the film surface is substantially smoother than films exhibiting columnar grain structures and ambient light is reflected, resulting in a high surface luster to the film. Thus, simple visual observation under ambient lighting is capable of distinguishing differences between the low luster of a film having a columnar texture and the high luster of a film having a non-columnar grain structure. Thus, as depicted in Figure 54, regions of higher luster are regions having no columnar texture, whereas regions of lower luster are regions of columnar growth. This luster difference is, however, is not well expressed and is difficult to observe when the film thicknesses are less than about 1 micron.

[00213] Figures 55 and 56 illustrate the relationships between cathode voltage and working gas pressure at a constant sputtering power of 180 W (Figure 55) and between sputtering power and working gas pressure at a constant cathode voltage of 600V (Figure 56). It will be readily appreciated that there is a nearly inverse relationship between the cathode voltage and the working gas pressure at a constant sputtering power, and a nearly linear relationship between the working gas pressure and the sputtering power at a constant cathode voltage. It has been found that the particular values for cathode voltage, sputtering power and working gas pressure are dependent upon the particular magnetron geometry, magnetic field strength, configuration of the magnetic field and the vacuum system. Thus, the values expressed in Figures 55 and 56 are valid for the particular reactor system employed. Nevertheless, those proficient in the sputtering arts will recognize that the relationships expressed in Figures 55 and 56 are valid irrespective of the particular magnetron and reactor system utilized. In accordance with the present invention it is preferable to employ a cathode voltage between about 500 - 1000 V, preferably between about 600 - 900 V, in order to obtain the benefits of lower working gas pressures attendant to this cathode voltage range.

[00214] It has been found that the inventive nitinol exhibits improved corrosion properties relative to conventional wrought nitinol tubing. A corrosion rate measurement was carried out by immersing a wrought nitinol tube (MINITUBES, France) and an inventive nitinol tube, of identical weight, in a 3M H2SO4 + Methanol solution for 15hrs at 37°C.

Both the wrought nitinol tube and a deposited tube were treated by the same passivation procedure. The weights and surface areas of each tube were measured before and after exposure to the acid bath. From these measurements, corrosion rate data was calculated as

2 4.18 μg/cm /hour for the wrought material and 1.54 for the deposited tube. Thus, the inventive vacuum deposited nitinol material exhibited greater resistance to corrosion. Based upon this data and based upon the well-known relationships between corrosion and fatigue resistance, it is reasonable to conclude that the inventive vacuum deposited nitinol tubes would also exhibit improved fatigue resistance when compared to wrought nitinol materials. [00215] Thus, in accordance with the present invention there is provided a vacuum deposition method for sputter depositing nitinol films having higher mechanical properties than those attainable or previously known in the art. The inventive vacuum deposition method entails controlling both the process parameters and the relationships between individual process parameters and depositing a nitinol film having high-strength mechanical properties. By carefully regulating the base pressure of the vacuum system, the quality and pressure of the process gas, the quality and finish of the substrate material, the temperature of the substrate, the power and voltage supplied to the cathode, the target material and material quality, the target surface temperature, and the throw distance, and balancing the relationships between these parameters, high-strength nitinol films having thicknesses between about 0.1 μm and 25 μm may be produced.

[00216] In addition to producing the high-strength nitinol films, the method of the present invention is readily adaptable to fabricating thicker films of biocompatible metals and pseudometals between 25 μm to 200 μm that are suitable for use as thicker graft materials and/or structural support elements such as stents.

[00217] While the invention has been described with reference to its preferred embodiment, those of ordinary skill in the relevant arts will understand and appreciate that the present invention is not limited to the recited preferred embodiment, but that various modifications in dimensions, geometries, fabrication methods, substrate material selection, manner of controlling the substrate surface, deposition methodology, and deposition process parameters may be employed without departing from the invention, which is to be limited only by the claims appended hereto.