Stent coating apparatus and method

An apparatus and method for coating abluminal surface of a stent is described. The apparatus includes a stent support, a coating device, and an imaging system. The coating device includes a solution reservoir and transducer assembly. The transducer assembly includes a plurality of transducers and a controller. Each transducer is used to generate focused acoustic waves in the coating substance in the reservoir. A controller is communicated to an image system to enable the transducers to generate droplets on demand and at the predetermined ejection points on the surface of the coating substance to coat the stent. A method for coating a stent includes stent mounting, stent movement, and droplet excitation.

FIELD OF THE INVENTION

The present invention relates to an apparatus for coating a stent and a method for coating a stent. More particularly, this invention provides an apparatus and method to generate uniform and controllable droplets that can be used to rapidly coat the abluminal surface (selective areas or entire outside surface) of a stent.

BACKGROUND

Percutaneous transluminal coronary angioplasty (PTCA) has revolutionized the treatment of coronary arterial disease. A PTCA procedure involves the insertion of a catheter into a coronary artery to position an angioplasty balloon at the site of a stenotic lesion that is at least partially blocking the coronary artery. The balloon is then inflated to compress against the stenosis and to widen the lumen to allow an efficient flow of blood through the coronary artery. However, restenosis at the site of angioplasty continues to hamper the long term success of PTCA, with the result that a significant proportion of patients have to undergo repeated revascularization.

Stenting has been shown to significantly reduce the incidence of restenosis to about 20 to 30%. On the other hand, the era of stenting has brought a new problem of in-stent restenosis. As shown inFIG. 1, a stent2is a scaffolding device for the blood vessel and it typically has a cylindrical configuration and includes a number of interconnected struts4. The stent is delivered to the stenosed lesion through a balloon catheter. Stent is expanded to against the vessel walls by inflating the balloon and the expanded stent can hold the vessel open.

Stent can be used as a platform for delivering pharmaceutical agents locally. The inherent advantage of local delivery the drug over systematic administration lies in the ability to precisely deliver a much lower dose of the drug to the target area thus achieving high tissue concentration while minimizing the risk of systemic toxicity.

Given the dramatic reduction in restenosis observed in these major clinical trials, it has triggered the rapid and widespread adoption of drug-eluting stents (DES) in many countries. A DES consisting of three key components, as follows: (1) a stent with catheter based deployment device, (2) a carrier that permits eluting of the drug into the blood vessel wall at the required concentration and kinetic profile, and (3) a pharmaceutical agent that can mitigate the in-stent restenosis. Most current DES systems utilize current-generation commercial stents and balloon catheter delivery systems.

The current understanding of the mechanism of restenosis suggests that the primary contributor to re-narrowing is the proliferation and migration of the smooth muscle cells from the injured artery wall into the lumen of the stent. Therefore, potential drug candidates may include agents that inhibit cell proliferation and migration, as well as drugs that inhibit inflammation. Utilizing the synergistic benefits of combination therapy (drug combination) has started the next wave of DES technology.

Strict pharmacologic and mechanical requirements must be fulfilled in designing the drug-eluting stents (DES) to guarantee drug release in a predictable and controlled fashion over a time period. In addition, a high speed coating apparatus that can precisely deliver a controllable amount of pharmaceutical agents onto the selective areas of the abluminal surface of a stent is extremely important to the DES manufactures.

There are several conventional coating methods have been used to apply the drug onto a stent, e.g. by dipping the stent in a coating solution containing a drug or by spraying the drug solution onto the stent. Dipping or spraying usually results in a complete coverage of all stent surfaces, i.e., both luminal and abluminal surfaces. The luminal side coating on a coated stent can have negative impacts to the stent's deliverability as well as the coating integrity. Moreover, the drug on the inner surface of the stent typically provides for an insignificant therapeutic effect and it get washed away by the blood flow. While the coating on the abluminal surface of the stent provides for the delivery of the drug directly to the diseased tissues.

The coating in the lumen side may increase the friction coefficient of the stent's surface, making withdrawal of a deflated balloon more difficult. Depending on the coating material, the coating may adhere to the balloon as well. Thus, the coating may be damaged during the balloon inflation/deflation cycle, or during the withdrawal of the balloon, resulting in a thrombogenic stent surface or embolic debris.

Defect formation on the stents is another shortcoming caused by the dipping and spraying methods. For example, these methods cause webbing, pooling, or clump between adjacent stent struts of the stent, making it difficult to control the amount of drug coated on the stent. In addition, fixturing (e.g. a mandrel) used to hold the stent in the spraying method may also induce coating defects. For example, upon the separation of the coated stent from the mandrel, it may leave some excessive coating material attached to the stent, or create some uncoated areas at the interface between the stent struts and mandrel. The coating weight and drop size uniformity control is another challenge of using aforementioned methods.

Another coating method involves the use of inkjet or bubble-jet technology. The drop ejection is generated by the physical vibration through an piezoelectric actuation or by thermal actuation. In an example, single inkjet or bubble-jet nozzle head can be devised as an apparatus to precisely deliver a controlled volume coating substance to the entire or selected struts over a stent, thus it mitigates some of the shortcomings associated with the dipping and spraying methods. Typically, this operation involves moving an ejector head along the struts of a stent to be coated, but its coating speed is inherently much slower than, for example, an array coating system which consists of many transducers and each transducer can generate droplets to coat a stent simultaneously. This coating apparatus enables to generate droplets at single or multiple locations simultaneously on demand, thus it allows to coat stent in a much faster and versatile way (e.g. line printing rather than dot printing).

Furthermore, nozzle clogging, which may adversely affect coating quality, is a common problem to spraying, inkjet, and bubble-jet methods. Cleaning the nozzles results in a substantial downtime, decreased productivity, and increased maintenance cost.

It has been shown that focused and high intensity sound beams can be used for ejecting droplets. It is based on a constructive interference of acoustic waves the acoustic waves will add in-phase at the focal point. Droplet formation using a focused acoustic beam is capable of ejecting liquid drop as small as a few microns in diameter with good reliability. It typically requires an acoustic lens to focus the acoustic waves.

The present invention provides a stent coating apparatus and method that overcome the aforementioned shortcomings from the conventional coating methods. The stent coating apparatus of the present invention can coat the abluminal surface of a stent at a high speed, and it can deliver a precise amount of coating material to the specific stent surfaces. Furthermore, the present invention does not use a nozzle, thus it eliminates the potential nozzle clogging issues.

According to the present invention, the stent coating apparatus includes a stent support, a coating device, and an imaging system. The stent support provides the mechanisms to hold a stent in place on a mandrel and to control the rotational and circumferential movement of the stent during the coating.

The coating apparatus includes a reservoir, a transducer assembly, and an ejection logic controller. The reservoir is used to hold a coating solution; a transducer assembly is used to generate acoustic energy to actuate the drop ejection from the surface of the coating solution; the ejection logic provides a control can over the position of droplet ejection. Transducers can be differentially turned on or off to steer the excitation of the droplets, and the droplet formation can be controlled only at the areas of the stent that need be coated. The advantage of this technique is it provides a reliable ejection of the fluids “on demand” without clogging the ejection aperture because the area of each ejection focal point is a relatively small region to the aperture.

The transducer assembly includes a plurality of transducers, RF drive device, and an ejection controller. Each transducer (e.g. piezoelectric transducer) can convert electrical energy into waves, such as ultrasonic waves. The transducer assembly generates acoustic waves and they propagate in the solution toward the liquid/air interface. Those waves are constructively interfered at a focal point of the solution surface, i.e., the waves will add in-phase at the focal point. The focused energy causes a droplet to be ejected from the surface of the coating solution. The wave frequency or amplitude can be used to adjust the droplet volume or droplet velocity.

In an embodiment of the invention, the constructively interfered waves are generated in certain patterns by controlling only portion of the transducers from the transducer arrays. Preferably, a switching system (or an ejection logic control) is linked to an imaging system to energize the transducers according to the stent strut position.

In an embodiment of the invention, the controller commands the transducer arrays to simultaneously eject droplets at multiple ejection points on the surface of the coating solution so that the stent can be coated simultaneously.

In an embodiment of the invention, the stent is preferably positioned above the ejector to receive the droplets generated from the surface of coating solution. In another embodiment, stent can be placed beneath the ejector. It will be appreciated by one of the ordinary skill in the art that embodiments of the invention enable to position the stent or the ejector in any orientation.

In an embodiment of the invention, the stent coating apparatus includes at least one assisted device, an imaging device. The image system is to track the stent strut location, to control the stent movement, and to communicate the information to the ejection logic controller. Accordingly, an imaging device with a feedback control is used to communicate to the stent holder controller to orient the stent to a particular position to receive the droplets generated by the corresponding coating device.

SUMMARY

Embodiments of the invention provide a coating apparatus and method that enable to coat stent outside surface selectively or simultaneously while avoiding nozzle clogging and coating defects caused by other conventional coating methods. Further, embodiments of the apparatus include a high speed and a nozzleless stent coating process.

In an embodiment of the invention, a method for coating a stent includes mounting a stent on a stent support, rotating the stent, and translating a stent in its longitudinal direction, and controlling a plurality of transducers to generate droplets at predetermined ejection points on the surface of a coating solution to coat the outside surface of a stent.

In an embodiment of the invention, that apparatus enables to generate droplets at single or multiple locations by using an ejection logic control to command the transducer arrays to generate droplets on demand. The transducer arrays used to generate the waves can be designed in a fashion to accommodate different stent geometries.

In an embodiment, the apparatus includes an optical feedback system to monitor and control the stent movement and, to communicate to the ejection logic controller to generate droplets to the selective surfaces of the stent.

In another embodiment, the apparatus is capable of adjusting the power, wave frequency or amplitude to control the drop volume or drop velocity respectively.

In an embodiment of the invention, a small multiple-reservoir system can be used to apply the same or different coating substances to the stent. The apparatus in this invention can coat the stent in a “line printing” fashion.

DETAILED DESCRIPTION

FIG. 2illustrates a stent coating apparatus10. The apparatus10includes a stent handling12, a coating device14, and an imaging system,56and58. The stent handling system12is to provide the supports to a stent16which is connected to motor26and motor27so as to control stent's circumferential and translational movements. The coating device14applies a coating to the stent16.

In the embodiment shown inFIG. 2, the stent support12includes a shaft20, a mandrel22, and an optional lock member24. The lock member24is optional if the mandrel22by itself can support the stent16. The support member20is connected to a motor26to rotate the stent in the circumferential direction, so as motor27to translate the stent in the longitudinal direction of the stent16, as depicted by the arrows28and29.

In this embodiment, the support member20includes a conical end portion30and a bore32for receiving a first end of the mandrel22. The first end can be threaded to screw into the bore32or can be retained within the bore32by a friction fit. The bore32should be deep enough to allow the mandrel22to mate securely with the support member20. The depth of the bore32can also be further extended to allow a significant length of the mandrel22to penetrate or screw into the bore32. The bore32can also extend completely through the support member20. This would allow the length of the mandrel22to be adjusted to accommodate stents of various sizes. The mandrel22may also include a plurality of ridges34that add rigidity to and support to the stent16during coating. The ridges34may have a diameter of slightly less than the inner diameter of the stent16. While three ridges34are shown, it will be appreciated by one of ordinary skill in the art that additional, fewer, or no ridges may be present, and the ridges may be evenly or unevenly spaced.

The lock member24also may include a conical end portion36. A second end of the mandrel22can be permanently affixed to the lock member24if the first end is disengageable from the support member20. Alternatively, the mandrel22can have a threaded second end for screwing into a bore38of the lock member24. The bore38can be of any suitable depth that would provide the lock member24incremental movement with respect to the support member20. The bore38on the lock member24can also be made as a through hole. Accordingly, stents of any length can be secured between the support member20and the lock members20and24. In accordance with this embodiment, the second end lock member24contains a through hole38enabling the second end lock member to slide over the mandrel22to keep the stent16on the mandrel22.

The coating device14shown inFIG. 2includes a reservoir40and a transducer assembly42. The reservoir40is used to hold a coating substance44to be applied to the stent16. The transducer assembly42is submerged in the reservoir40. The transducer assembly42generates acoustic energy to eject droplets from the surface46of the coating solution44to coat the stent16. Preferably, the locations of the ejection points on the surface46of the coating substance44are matched to the stent strut areas that need to be coated.

The reservoir40may have any suitable configuration and may be disposed at any suitable location. For example, the reservoir40may have a cylindrical, elliptical or parallelepiped configuration. Preferably, the reservoir40encompasses the entire stent16so that droplets ejected from the surface46can reach all areas of the stent16. Alternatively, the reservoir40may cover only an area of the stent to be coated. In a preferred embodiment, the reservoir40is positioned directly underneath the stent. Also, a short distance between the stent and the surface of reservoir46is maintained to ensure a stable droplet ejection.

As shown inFIG. 2, the transducer assembly42includes a plurality of transducers48and a controller50that is programmed to control the transducers48. Each transducer48is used to generate the acoustic energy in the form of sound or ultrasound waves. Each transducer48preferably is a piezoelectric device, although it can be any other device suitable for generating ultrasound waves. The use of focused acoustic beam to eject droplets of controlled diameter and velocity from a free-liquid surface are well known in the art.FIG. 3is a schematic diagram to show the mechanism of generating the droplet on demand using transducer arrays.

The controller50may be used to control the frequency, amplitude, and phase of the waves generated by each transducer48and to turn on or off the power supplied to the transducer48. To generate a droplet at a predetermined point on the surface46, the controller50controls the transducers48to generate waves that constructively interfere at this predetermined point. The focused acoustic energy causes a droplet to be ejected from the surface46of the coating substance44to coat the stent16. Adjusting the frequency and amplitude of the ultrasound waves allows control over the ejection speed and volume of the droplet.

FIG. 4depicts the mechanism of generating a droplet from the surface of a coating substance. As illustrated inFIG. 4, a coating substance44is contained in a reservoir (not shown); also, there are nine transducers48submerged in the coating substance44. The transducers48are used to generate focused in-phase waves at a predetermined ejection point54on the surface46of the coating substance44. In other words, the waves are coherently constructed (in phase) at the ejection point (focal point)54. The focused (through the acoustic lens) acoustic energy creates the required pressure at the ejection point54, to eject a droplet52from the surface46onto the stent surface. In order for the waves to arrive at the ejection point54in phase, the transducers48should generate the waves at different times. In the example shown inFIG. 4, each of the first and ninth transducers, which are farthest from the ejection point54, should first generate a wave. The fifth transducer, which is the closest to the ejection point54, is the last to generate a wave. The precise timing for progressively generating the waves can be determined by a person of ordinary skill in the art and will not be discussed herein.

According to the present embodiment, as illustrated inFIG. 2, stent16is coated line by line as the stent rotates. The droplet ejection is controlled in a linear fashion and the droplet is generated only in the section that stent strut is detected. Preferably, these ejection points are aligned to stent's longitudinal direction, and the coating substance is received only on the stent's outside surfaces. The ejection points are determined through the image controllers to verify if a stent strut is present. Thus, the ejection can be excited accordingly. Excitation of drops can start from one end and ending at the other end, or the droplets can be fired in segment or in all.

The droplet formation can be generated by singe or combination of any number of transducers48in the reservoir40. In some embodiments, the number of transducers used to generate each droplet may be seven. For example, the first droplet may be generated by transducers Nos.1to7, the second droplet by Nos.2to8, the third droplet by Nos.3to9, . . . and so on. In some other embodiments, the number of transducers for generating a droplet may vary from droplet to droplet. For example, the first droplet may be generated by nine transducers, the second droplet by five, the third droplet by15, . . . and so on. Preferably, the transducers used to generate a droplet are symmetrically arranged about the ejection point from which the droplet is ejected. Non-symmetrically arranged transducers tend to eject a droplet in a direction oblique to the surface of the coating substance. But one of ordinary skill in the art recognizes that an asymmetrical arrangement of the transducers can also be utilized to generate any specific ejection patterns by adjusting the timing, amplitude, or frequency of waves.

One preferred embodiment as shown inFIG. 2, the transducers48are arranged linearly and evenly spaced. In general, however, the transducer array can be arranged in any suitable manner. For example, instead of being arranged in a single row as shown inFIG. 2, the transducers may be arranged in two or multiple parallel rows. Additionally, the total required number of transducers48included in the transducer assembly42can vary depending on the application. For example, the number of transducers may range from 5 to 10,000, from 10 to 2,000, from 20 to 1,000, from 30 to 600, or from 40 to 400.

The stent coating apparatus10shown inFIG. 2is used to illustrate an example of using only one coating device14to coat the stent. This apparatus can be easily expanded to contain a dual-reservoir or multiple-reservoir coating system that will allow to accelerate the coating speed or it will allow to apply different formulations onto a stent. For example, as shown inFIG. 5, a stent coating apparatus110includes two coating assemblies114aand114bthat are laterally arranged next to each other. Each assembly may contain different therapeutic agent. The therapeutic agent can be applied over the stent in sequence (i.e. layer by layer) to achieve a synergist effect. For example, the first coating assembly114ais used to apply a layer of drug A over the stent16, while the second assembly114bis used to apply another layer of drug B on top of drug A layer.

As illustrated inFIG. 2, the stent coating apparatus10may include a first vision device56that images the stent16before or after the coating substance44has been applied to the stent16. The first imaging device56, along with a second imaging device58located a distance from the stent16, are both communicatively coupled to the controller50of the transducer assembly42. Based on the image provided by the imaging devices56,58, the controller50actuates the ejection of the droplets to coat only selected areas of the stent16accordingly.

After a section of the stent16has been coated, the coating device14may be stopped from dispensing the coating substance, and the imaging device56may begin to image the stent section to determine if the section has been adequately coated. This determination can be made by measuring the difference in color or reflectivity of the stent section before and after the coating process. If the stent section has been adequately coated, the stent coating apparatus10will begin to coat a new section of the stent16. If the stent section is not coated adequately, then the stent coating apparatus10will recoat the stent section.

In an embodiment of the invention, the imaging devices56,58can include charge coupled devices (CCDs) or complementary metal oxide semiconductor (CMOS) devices. In an embodiment of the invention, the imaging devices can be combined into a single imaging device. Further, it will be appreciated by one of ordinary skill in the art that placement of the imaging devices56,58can vary as long as the devices have an acceptable view of the stent16.

During the operation of the stent coating apparatus10illustrated inFIG. 2, the stent16is first mounted on the mandrel22of the stent support12. The stent16is then rotated about its longitudinal axis by the motor26of the stent support12. Once the stent16starts to rotate, the controller50of the coating device14commands the transducers48to generate in phase acoustic waves at one or more predetermined ejection points on the surface46. Droplets are ejected at the focal points and get dispensed onto the stent16. Additionally, the droplet volume can be tuned by adjusting the frequencies, and the drop velocity can be controlled by changing the wave amplitude. Furthermore, one or two imaging devices56,58may be used to generate an image of the stent16to be used to direct the droplets to selected areas of the stent16.

Although the transducer assemblies42of the above-described embodiments are placed inside the reservoir40and submerged in a coating substance during operation, it is possible to place a transducer assembly outside of a reservoir.FIG. 6illustrates a stent coating apparatus110that includes a reservoir40and a transducer assembly142that is placed outside of the reservoir40. In some embodiments, it may be preferable to place only some, but not all, of the transducers of the transducer assembly outside of the reservoir. The stent coating apparatus110may further include an acoustic lens160placed preferably between each transducer148and the reservoir40. Each acoustic lens160may have any suitable configuration, such as a concave configuration. The acoustic lenses160may be in direct contact with the coating substance or indirectly in contact with the coating substance through a coupling fluid162(external to the solution reservoir). The transducer assembly142may include (or may be coupled to) drive electronics, such as an ejection control50, an RF amplifier, RF switches, and RF drives164.

Furthermore, although the embodiment shown inFIG. 6has only one reservoir40, one or more additional reservoirs may be added, and each reservoir may have one or more transducers. In the embodiment210shown inFIG. 7, for example, there is a reservoir240for each transducer148.

The present invention offers many advantages over the prior art. For example, the present invention has the ability of coating stent abluminal surface only. A controlled volume of drops are generated and precisely delivered to the selective stent struts, thus it provides a better therapeutic control and it avoids the coating defects that are occurred in spraying and dipping methods. Additionally, the coating speed can be significantly increased through the transducer arrays design that enables coating the stent at multiple locations at a time. Furthermore, the present invention utilizes a nozzleless coating apparatus, thereby it eliminates the nozzle clogging issue which is a common issue to many conventional coating methods.