Method and apparatus for coating a stent

ES 2 322 865 T3

DESCRIPTION

Procedure and apparatus for coating a stent.

Field of the invention

The present invention relates to coated medical devices intended to be deployed in vivo and, in particular, to a method and device suitable for use, just prior to implantation, for the selective application of a medical coating to a medical device. implantable, for example, a stent.

Definitions

The term "prosthesis" refers to any one of many applications with medical coatings including, but not limited to, coronary stents, peripheral vascular stents; devices for abdominal aortic aneurysms (AAA), stents and biliary catheters, catheters and stents for TIPS, vena cava filters, vascular filters and distal clamping devices and occlusion aids / filters for embolisms, vascular grafts and stent-grafts , gastroenteral tubes / stents, gastroenteral and vascular anastomotic devices, urinary catheters and stents, surgical and wound drains, radioactive needles and other permanent metal implants, bronchial tubes and stents, vascular coils, vascular protection devices, valves and tissue rings and for mechanical prosthetic hearts, arterio-venous shunts, arterio-venous access grafts, surgical tampons, dental implants, cerebrospinal fluid shunts, electrodes and probes of pacemakers, suture material, wound healing, tissue closure devices including thread, staples, surgical clips, etc ..., IUDs and associated pregnancy control devices, eye implants, tympanoplasty implants, hearing aids including cochlear implants, implantable pumps, eg insulin pumps, implantable chambers and other diagnostic devices, drug delivery capsules, ventricular assist devices left (LVAD) and other implantable vascular and heart support systems, permanent vascular access catheters and associated devices, for example, connections, maxillofacial implants, orthopedic implants, for example, joint replacement, surgical devices for the spine and trauma treatment, implantable devices for cosmetic and plastic surgery, implantable meshes, for example, for hernias or for uro repair -vaginal, brain disorders and gastrointestinal problems.

The term "drip-on-demand" as used herein refers to any active or passive release of a predetermined drop or number of drops equivalent to a desired amount of coating material, eg, a material coating to be put on a prosthesis. Drip-on-demand also refers to the launching of jets in which a sequence of drops is released. An example of "drip-on-demand" is the piezoelectric "drip-on-demand" technology manufactured by Ink Jet Technology, Inc. of San Jose, California, which provides applicators for a wide range of coating applications. The micromachined ceramic materials design of this technology is robust and chemically inert to almost all types of fluids and coatings and is compatible with a wide range of fluids that have extreme pH values ​​or strong solvent characteristics. Non-Newtonian fluids are also compatible with such devices due to the internal design of the applicator that allows laminar flow of the fluid. With a potential for high temperature operation and an integrated heater, the piezoelectric drip-on-demand applicators are compatible with a wide range of coating materials. In addition, acoustic droplet delivery devices such as those described by Xerox Corporation on the website http://www.parc.xerox.com/research/dhl/projects/dropletdispensing/acoustic.ht can also be used.

The term "detector" or "sensing" refers to any device or procedure that uses energy, such as magnetic, electrical, heat, light, etc. to determine if a target has been located at a desired location on the prosthesis and signals the applicator to drip-as-demand or identifies a location as one to be coated. The detector may or may not determine a location of the applicator relative to the target to provide feedback for positioning the applicator. The detector determines the points in the coordinate table for desired locations on the prosthesis by providing signals to the applicator controller that are used immediately or stored as coordinate tables. Examples of detectors are light sensitive devices, such as CCD area cameras, CCD line cameras, high resolution CMOS area cameras or devices that can capture light reflected or transmitted by the prosthesis and electrically sensitive devices such as capacitive detectors. .

The term "applicator" or "apply" refers to any configuration, equipment, or procedure for placing a coating material on a surface from a reservoir such as a point source including, but not limited to, a nozzle, a dispenser, or a tip, or a multi-point source. An example of an applicator is a drip-on-demand ink jet.

The term "skip-free" refers to the translation and delivery of drops-on-demand that is synchronous or nearly synchronous and / or simultaneous or nearly simultaneous. Unlike the Freestyle movement, which requires a stop for the validation of the anterior and posterior movement with respect to the prosthesis, "no jumps" continues until the next movement without the validation stage. Fig. 13 illustrates an example of no-jump drip-on-demand with an embodiment in which the axis of rotation 700 is stationary and the applicator moves on the Z axis. A servo controller 705 directs the Z unit 710 that is coupled to the applicator 725 while monitors the speed and location of the applicator 725 via a feedback device 715. The servo controller 705 keeps the Z 710 unit within the

ES 2 322 865 T3 predetermined speed limits required and signals the applicator controller 720 to activate the drip-on-demand applicator using data from the feedback device 715 in reference to the coordinates of the prescan performed by a detector that determines the points that they have to be coated. In this procedure, the validation of the Z position of the applicator 725 is performed in real time by the servo controller 705. The servo controller 705 interacts with the axis of rotation to determine the next location based on the last location and the time it takes for the Z unit 710 to move the applicator 725 to the next location. The feedback device 715 provides feedback, that is, an internal logic procedure based on the servo controller, and is not related to the actual location relative to the prosthesis and is therefore not a validation step, as discussed above. In alternative embodiments, the servo controller 705, the Z unit 710, the feedback device 715, the Z location applicator controller 720, and the applicator 725 may all be included in the application control module (not shown).

The term "freestyle" refers to a movement of an applicator over a portion of a prosthesis to be coated that needs validation according to a predetermined pattern selected by the user and / or a feedback loop of the position of the applicator with respect to to the portion of the prosthesis to be coated. Validation takes place prior to supply of coating material. In one embodiment, the freestyle movement moves the applicator above a predetermined position based on a pattern selected by the user. The position of the applicator is verified relative to the prosthesis and a new location is calculated. The applicator is moved to a new and more precise location. The applicator delivers the coating material and then moves to the next predetermined location based on the pattern selected by the user.

It is noted that, as used in this specification and appended claims, the singular forms "a", "an" and "the" include plural referents unless they are expressly and unequivocally limited to one referent. Thus, for example, the reference to "one applicator" includes two or more applicators, but that "n is an integer from 1 to 60" means that n is an integer because it is limited to an integer. It is also noted that, as used herein, the term "polymer" is intended to refer to oligomers, homopolymers, and copolymers. The term "therapeutic agent" is intended to refer to drugs, therapeutic materials, diagnostic materials, inert ingredients, active ingredients, and inactive ingredients.

For the purposes of this specification and appended claims, unless otherwise indicated, all numbers expressing amounts of ingredients or percentages or proportions of other materials, reaction conditions, etc., used in the specification and claims are they are to be considered as modified in all examples by the term "about". Accordingly, unless otherwise indicated, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending on the desired properties that the present invention seeks to obtain. At a minimum, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be interpreted at least in light of the number of significant digits indicated and by applying common rounding techniques.

Although the numerical ranges and parameters that are within the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are indicated as precisely as possible. Any numerical value, however, inherently contains certain errors that necessarily result from the standard deviation found in the measurements of their respective tests. Furthermore, it should be understood that all ranges disclosed herein encompass any and all subranges contained therein. For example, an interval from "1 to 10" includes any and all subintervals between (and including) the minimum value of 1 and the maximum value of 10, that is, any and all subintervals that have a minimum value equal to or greater than 1 and a maximum value equal to or less than 10, for example, from 5.5 to 10.

Background of the invention

The practice of coating implantable medical devices with an active or inactive synthetic or biological agent is known. Various methods have been proposed for applying such a coating. US Patent 5,922,393 to Jayaraman suggests soaking or immersing the implantable device in a bath of liquid medications, while US Patent 6,129,658 to Delfino et al. suggests soaking it in a shaking bath. Devices that introduce heat and / or ultrasound energy in combination with the drug bath are disclosed in US Patents 5,891,507 to Jayaraman and 6.25.4BI to Alt. US Patent 6,214.1 B1 to Taylor et al. suggests spraying medications through pressurized nozzles.

Initially, such coatings were applied at the time of manufacture of the medical device. For various reasons, such as the short shelf life of some drugs along with the period of time from manufacture to implantation and the possible decision of the medical personnel involved regarding the specific drug and dosage to be used based on the condition. of the patient at the time of implantation, a need has arisen for technologies that allow the application of a coating just prior to implantation. In US Patent 6,309,380BI to Larson et al. It is disclosed to wrap the implantable device with a film formed with medicaments. US Patents 5,871,436 to Eury, 6,6,454 to Berg et al. and 6,1171,232BI to Panpandreou et al. suggest immersion or soaking in a medicated bath just before implantation. US Patent 6.3,551BI to Wu provides a chamber for a bath for use with a specific implantable device such as a stent deployed in the balloon of a catheter.

ES 2 322 865 T3

Each of the procedures and devices intended for use just prior to implantation, listed above, deposits the coating material on any and all surfaces that are exposed to the coating. This can result in the deposition of coating material on surfaces where coating is unnecessary or unwanted. Additionally, the coating can crack or peel when the implantable device is removed from the implantation set. An example of this would be a stent deployed on a catheter balloon. As the balloon inflates and the stent expands into position, the coating can crack along the interface between the stent and the balloon. These cracks can lead to the detachment of a portion of the coating from the stent itself. Similar problems can occur in cases where the coating technique fails to avoid inadvertent overlap with the edges, internal surfaces along the edges, of various devices, eg, stent struts. This, in turn, can affect the medicinal efficacy of the coating and adversely affect the entire medical procedure.

The use of ink jet technology to apply a liquid to a selected portion of a surface is known. In the article “Applications of Ink-Jet Printing Technology to BioMEMS and Microfluidic Systems”, presented at the SPIC Conference on Microfluidics and BioMEMS, October, 2001, the authors, Patrick Cooley, David Wallace and Bogdan Antohe, provide a fairly detailed description. of inkjet technology and the variety of its medically related applications (the article "Cooley"), http: // www. microfab.compapers / papers_pdf / spiebiomems_O1_reprint.pdf.

A related device is disclosed in US Patent 6,001,311 to Brennan, which uses a two-dimensional set of nozzles to deposit a plurality of different liquid reagents into receiving chambers. In Cooley's paper and Brennan's device, selective material application is based on an objective predetermined location for the deposit, rather than on a "subjective location", since it needs to meet the requirements of a specific application procedure. Regarding the application of coatings applied to medical devices with ink jet applicators, it is possible to coat only a chosen portion of a device, such as only the stent mounted on a catheter, but not the catheter itself. This type of procedure using current technologies may, however, require providing complex data files, such as a CAD image of the device to be coated, and ensuring that the device is installed on a coating equipment. Precise mode so that it is oriented exactly the same as in the CAD image.

Other systems using inkjet applicators apply the coating in a "freestyle" procedure. Freestyle points are determined by a user-selected pre-programmed pattern that is unique to the particular shape or contour for the type of prosthesis and the desired coating to be achieved, much like a vector-based impression approach. The ink jet nozzle or prosthesis is moved in three dimensions with the help of a motion control system. The motion control system allows the ink jet nozzle to move over portions of the prosthesis to be sprayed. Alternatively, a real-time photograph can be taken with a camera to determine the position of the ink jet nozzle relative to the prosthesis. Based on feedback from the nozzle location, the ink jet applicator can be controlled by activating the spray, moving the ink jet nozzle, and / or moving the prosthesis to fit the pattern to better fit the actual prosthesis.

This type of system is especially ineffective because the user-selected pre-programmed pattern fails to account for the inherent variability in the prosthesis surface. In a non-limiting embodiment, for example, a stent snapped around a balloon catheter will not be snapped on so that it has the same surface area each time. Pressure fixation cannot be determined at the factory based on the stent manufacturer's specifications. In addition, the use of this type of feedback loop serves only as a "first impression" to control spray, nozzle position and / or prosthesis position, and freestyle systems therefore increase the time required to apply the coating. In the operating room, this delay is undesirable because many types of coatings, eg, paclitaxel, rapamycin, or various other pharmaceuticals or bioactive agents have to be applied to the stent pressure attached to the balloon catheter immediately prior to surgery.

From WO03 / 092909A1 a method and a corresponding device are known for selectively applying a medical coating to an implantable medical device suitable for use in an operating room just prior to implantation. A device for use with a stent deployed in a balloon of a catheter is disclosed. The device is configured to apply a medical coating only to the surface of a stent. This is done by using a drip-on-demand inkjet printing system in conjunction with an optical scanning device.

The importance of drug-loaded delivery prostheses may offer time and cost saving advantages. Studies have been conducted to show the importance of delivering the correct drug dose density in coronary stents to avoid stenosis by application of paclitaxel or rapamycin. Kandazari, David E. et al., Highlights from American Heart Association Annual Scientific Sessions 2001: November 11-14, 2001, American Heart Journal 143 (2), 217-228, 2002; Hiatt, Bonnie L. et al., Drug-Eluting Stents for Prevention of Restenosis: In Quest for the Holy Grail, Catheterization and Cardiovascular Interventions 55: 409-417, 2002; Kalinowski, M. et al., Paclitaxel Inhibits Proliferation Of Cell Lines Responsible For Metal Stent Obstruction: Possible Topical Application In Malignant Bile Duct Obstructions, Investigational Radiology 37 (7): 399-404, 2002. Other studies have shown how dose precision is related with the cytotoxicity of the coating drugs. Liebmann, JE and

ES 2 322 865 T3 col., Cytotoxic Studies Of Paclitaxel (Taxol) In Human Tumor Cell Lines, Br. J. Cancer, 68 (6): 1104-9, 1993; Adler, LM et al., Analysis Of Exposure Times And Dose Escalation Of Paclitaxel In Ovarian Cancer Cell Lines, Cancer, 74 (7): 1891-8, 1994; Regar, E. et al., Stent Development And Local Drug Delivery, Br. Med. Bulletin, 59: 227-48, 2001. See also the website http://www.tctmd.com/expert-presentations: Farb, A., Comparative Pathology Of Drug Eluting Stents: Insights Into Effectiveness And Toxicity From Animal Lab, CRF Drug-Eluting Stent Symposium 2002; Grube, E., Taxol-Eluting Stent Trials, ISET 2002 Miami Beach, March 19-23, 2002 (The effect of taxol on the edges of the stent and dose response screening); Carter, Andrew J., Sirolimus: Pre-Clinical Studies - Evaluation Of Dosing, Efficacy And Toxicity, TCT September 2001.

Summary of the invention

The present invention is a method and device, which is suitable for use in an operating room just prior to implantation, for the selective application of a medical coating to an implantable medical device, eg, a stent.

The present invention provides optical scanning of an object to produce a digitized representation of the object; processing the digitized representation to distinguish a first portion of the object from a second portion of the object; determining a first set of locations in a first coordinate system for a plurality of locations in the first portion of the object; and converting the first set of locations in the first coordinate system to a corresponding second set of locations in a second coordinate system.

In one embodiment, each set in the first set of locations in the first coordinate system comprises a one pixel location in the digitized representation; and each set in the second set of locations in the second coordinate system comprises a linear component and a radial component.

In another embodiment of the present invention, a method of coating a medical device includes generating an image of the medical device; processing the generated image to determine a topology of the medical device; defining a first plurality of locations in a given topology in which at least one drop of a coating material is to be placed; converting the first plurality of locations to a corresponding second plurality of locations, each location of the second plurality of locations representing a physical location on the medical device; and deposition of at least one drop of coating material at each location in the second plurality of locations.

According to yet another embodiment of the present invention, the coating is applied based on a local geometric characteristic of the stent. Accordingly, a method optically scans an object to produce a digitized (electronic) representation of the object; processes the digitized representation to distinguish a first portion of the object from a second portion of the object; identifies of the at least one feature area of ​​the first portion of the object and determines a type of the at least one identified feature area; and determines at least one feature of a coating material to be put into the at least one identified feature area of ​​the first portion of the object based on the determined type.

Brief description of the drawings

The invention is described herein, by way of example only, with reference to the accompanying drawings, in that:

fig. 1 is a side elevation section of a stent covering device constructed and operated in accordance with the teachings of the present invention;

fig. 2 is a perspective sectional view of the stent covering device of FIG. 1;

fig. 3 is a perspective detail of an alternate movable applicator head constructed and operating in accordance with the teachings of the present invention, shown herein configured with disposable coating applicators;

fig. 4 is a perspective sectional view of the stent covering device of FIG. 1, showing a detachable housing section separated from the housing base section;

fig. 5 is a perspective detail of an upper stent holding element, constructed and operating in accordance with the teachings of the present invention;

fig. 6 is a side elevation of the stent covering device of FIG. 1, showing the total length of a catheter that is held by the clamping antenna;

fig. 7A is a flow chart of a non-limiting embodiment of a method for coating a stent in accordance with the present invention;

ES 2 322 865 T3 FIG. 7B is a flow chart of the method known in the art for coating a stent;

fig. 8 is a flow chart of a non-limiting embodiment of the pre-coating process according to the present invention;

fig. 9A is a flow chart of a non-limiting embodiment of the coating process according to the present invention;

fig. 9B is a flow chart of a procedure for coating a stent using a preselected library;

fig. 9C is a flow chart of a procedure for coating a stent using real-time imaging;

fig. 10 is a flow chart of a non-limiting embodiment of the post-coating process according to the present invention;

fig. 11 illustrates a detail of a stent on a balloon catheter and an enlarged perspective of the surface of the stent to be coated;

fig. 12 illustrates a flow chart of a non-limiting embodiment of raster overlay without the use of pre-scan or post-scan;

fig. 13 illustrates a flow chart of one embodiment of applicator "skip-free" translation and delivery of coating material. In alternative embodiments, the servo controller 705, the Z unit 710, and the Z location feedback device 715 may all be included in the application controller 720;

fig. 14 is a functional block diagram of one embodiment of the present invention;

fig. 15 is a block diagram of a computing device;

fig. 16 is a diagram of one embodiment of the present invention;

fig. 17 is a flow chart of a coating process according to one embodiment of the present invention;

fig. 18 is a captured image of a stent;

fig. 19 is a flow chart of a coating process according to one embodiment of the present invention;

fig. 20 is a schematic block diagram of the coating mechanism according to an embodiment of the present invention;

fig. 21 is a representation of the helical phase shifted coating according to one embodiment of the present invention;

figs. 22A-22C are representations of a scanned stent in accordance with one embodiment of the present invention;

fig. 23 is a flow chart for a coating according to geometric characteristics according to an embodiment of the present invention;

figs. 24A and 24B are representations of geometric regions of a stent;

fig. 25 is a flow chart of a calibration procedure according to one embodiment of the present invention;^Y fig. 26 is a schematic representation of a scanning procedure in accordance with one embodiment of the present invention.

Detailed description

The present invention is a method and device, which is suitable for use in an operating room just prior to implantation, for the selective application of a medical coating to an implantable medical device, eg, a stent.

The principles and operation of a coating device according to the present invention can be better understood with reference to the drawings and the accompanying description.

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By way of introduction, the embodiment discussed herein is a device for applying a medical coating to a stent deployed on a catheter, the coating being applied just prior to implantation and, if desired, in the operating room. The use of optical scanning devices allows a processing unit to distinguish between the surface area of ​​the stent and the surface area of ​​the catheter. The processing unit selectively activates the coating applicator to apply the coating basically only to the stent and not to the balloon or other portion of the catheter. The coating applicator discussed herein is, by way of non-limiting example, a pressure pulse driven droplet ejection system with at least one nozzle. A readily available pressure pulse driven drop ejection system, which is well suited to the present invention, is a drip-on-demand ink jet system. It should be noted, however, that any coating application system that can be selectively activated is within the scope of the present invention. Although the discussion herein is specific to this embodiment, which is intended for use in an operating room, among other places, this embodiment is intended as a non-limiting example of the principles of the present invention. The variety of applications suitable for the principles of the present invention will be clearly apparent to those skilled in the art. The device described herein, as a non-limiting example, with minor adaptations in terms of the object holding element and the choice of fluid coating materials, is very suitable for a wide range of objects to which the coating is applied. .

Referring now to the drawings, fig. 1 illustrates a device 1 for applying a coating to a stent 2 that is deployed on a catheter 4. The coating applied can be a synthetic or biological agent and active or inactive. The perspective view of FIG. 2 is on the same side as that of the device in fig. 1 and, therefore, to better understand the description of elements of the device, reference will be made to fig. 2. The catheter 4 is placed in an application compartment 40 and is held in position by a rotary catheter clamping base 6 and an upper rotary catheter clamping element 8, configured for basically continuous rotation, that is, they can complete a plurality 360 ° full rotations, as needed, during the coating procedure. The actual rotation can be basically totally continuous (no stops) or intermittent. The upper catheter holding element will be discussed in detail below with reference to FIG. 4. The closed application compartment provides a sterile environment in which the coating procedure is performed. Rotation of the catheter clamp base and upper catheter clamp is driven and synchronized by a motor and gear system including gear sets 12, 14, 16 and a shaft 18 (see also Fig. 2 ). Alternatively, the gears can be replaced by drive belts or any other mechanism that maintains a synchronized mechanism, for example, two DC servo motors driven master / slave by the system controller. The excess length of the catheter is held by a clamping antenna 22, as illustrated, by way of non-limiting example, in FIG. 6. As noted above, the object holding elements can be modified to hold any suitable object for coating in accordance with the teachings of the present invention.

The coating is applied by a drip-on-demand inkjet system in conjunction with an optical scanning device 32 and a processing unit. As the object rotates through the object clamp, the optical scanning device scans the surface of the object. The output of the scanning device is used by the processing unit to determine whether the area of ​​the surface currently aligned with the coating applicator is of the type of surface to be coated. When it is determined that the surface type is aligned with the coating applicator, the processing unit activates the coating applicator and the coating is delivered. The embodiment shown here includes three ink jet coating applicators 30a, 30b, and 30c and two optical scanning devices 32a and 32b. Optical scanning devices can be configured to generate a digital output or an analog signal which, in turn, is analyzed by the processing unit. It should be noted that the number of coating applicators and scanning devices can be modified to meet design or application requirements.

The three coating applicators and the two optical scanning devices are mounted on a movable head 34 of the applicator. The position of the applicator head 34 within the application compartment and therefore the spatial relationship between the coating applicator and the stent, or other object to be coated, is regulated by the application control module 36 that is, in turn, controlled by the processing unit. Repositioning of the applicator head 34 is performed vertically by turning the vertical positioning screw 60 together with the guide shaft 62 and horizontally by turning the horizontal positioning screw 64 together with the guide shaft 66. Vertical repositioning along with rotation of the object allows the coating applicator to basically cross the entire surface of the object that needs coating.

The flowable coating material is stored in three fluid reservoirs 50a, 50b, and 50c (see fig. 2) and is supplied to the respective coating applicators via flexible fluid supply tubes 52a, 52b, and 52c (see fig. 2). . In general use, each of the fluid reservoirs contains a different coating material, therefore, each coating applicator will deposit a different coating material on the stent or other object being coated, as needed. Furthermore, a plurality of layers can be applied, each layer being of a different coating material and, if necessary, of a different thickness. Thus, at the time of coating, a single suitable coating material can be chosen from the materials provided or a combination of coatings can be chosen. It should be noted that although the fluid reservoirs are shown here in a compartment within the device housing, this need not always be the case, and the reservoirs may be external to the housing.

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It should be noted that, alternatively, the ink jet system may be deployed in a disposable housing that also includes a fluid reservoir filled with coating material. The fluid reservoir can be a closed volume that is integrated into the disposable housing or it can be a cartridge filled with the liner that is inserted into a receiving cavity in the disposable housing. In this case, as illustrated in fig. 3, the movable applicator head 34 is configured to accept one or more of the disposable housings 36a, 36b, and 36c, which, in turn, house inkjet coating applicators 38a, 38b, and 38e, respectively. Fluid reservoirs (not shown) for each applicator are housed in that portion of the disposable housing that is deployed within head 34 of the movable applicator.

Fig. 4 illustrates how housing base section 70 and housing detachable section 72 are interconnected. The two sections are held together by insert pins 74, which extend from the detachable section of the housing to corresponding holes 76, located in the base section of the housing and which engage the latch mechanism 78 to the latch element 80. The separation of the two sections is accomplished by pressing the release button 84, which lifts the end 82 of the latch thereby releasing the latch element. The two sections are then separated. The application compartment is defined by a top, a floor and three walls located in the detachable section of the housing and a wall on the base section of the housing. The detachable sections of the housing are configured to be disposable or, if desired, easily cleaned and re-sterilized.

The detail in fig. 5 illustrates the components of the upper catheter holder. Extending from basically the center of the rotating base plate 90 is a threaded tube 92. Tube 92 is the outer end of the passageway through which the catheter tip with the attached stent is inserted to deploy the stent into the delivery compartment of the coating device. The tube is cut lengthwise several times, to create threaded sections 98, here six, that are configured to bend outward from the center. The clamping disc 94 has a correspondingly threaded central hole for deployment over the tube 92 so that when the clamping disc is brought to a position proximal to the base plate, the threaded sections near the end of the tube will bend outward. thus enlarging the diameter of the opening. The fastener 96 also has fingers 100 that are divergently bent. During operation, the fixation element unfolds around the catheter, which then passes through the tube into the delivery compartment. When the catheter has been positioned on the catheter holding base, the fixation element is, at least partially, inserted into the opening of the tube. The clamping disc 94 then rotates around the tube and is brought to a position proximal to the end of the tube; The outwardly bending sections of tube 98 are then brought to an unbent state, thereby decreasing the diameter of the opening. The decrease in the diameter of the tube opening pushes the fingers 100 of the fixator against the catheter, thus holding the catheter in place.

A non-limiting example of the stent coating procedure performed by the device described above would be as follows:

1. The fluid reservoirs are filled with the necessary fluid coating materials.

2. Coating parameters are entered into the processing unit. The parameters may include, by way of non-limiting example, the coating material to be applied, the thickness of the coating, the number of multiple layers of different coating material, the order in which the coating materials are to be applied. layers and the thickness of each layer. The parameters can be determined by the physician at the time the coating is applied or the parameters can be pre-set, such as those determined by medical regulations. In the case of pre-set parameters, the physician would simply enter a "start" command.

3. The catheter is positioned in the delivery compartment and the upper catheter clamp is tightened.

Four. As the catheter rotates, the optical scanning device scans the catheter surface to distinguish between the balloon surface and the stent surface.

5. When a portion of the stent surface is detected and determined to be aligned with the appropriate coating applicator, the processing unit selectively activates the applicator, thus ejecting the necessary amount of coating material, which is basically deposited only on the surface. of the stent.

6. Throughout the coating procedure, the position of the applicator head is adjusted as necessary. This adjustment can bring the coating applicator closer to, or further from, the stent surface and can adjust the vertical deployment of the coating applicator, thus allowing the coating of different areas of the stent surface. In addition, if a different flowable coating material is needed for a different layer of the coating, the coating applicator for that particular coating material can be properly aligned for the deposition of the new coating material on the stent.

7. When the veneering procedure is complete, the stent-coated catheter is removed from the device and the stent is ready for implantation.

8. The detachable section of the housing is removed and can be cleaned and sterilized for reuse, or simply discarded.

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It should be noted that in some cases it may be desirable to coat basically the entire surface of the object being coated. This can be done in at least two ways. The object itself can have only one type of surface. Alternatively, the scanning device can be configured to provide adjustable scanning sensitivity. In the latter case, the sensitivity of the scanning device can be adjusted so that its output is indicative of only one type of surface and the processing unit cannot distinguish between different types of surfaces.

The flow chart of fig. 7A illustrates a process for coating a prosthesis 102 based on the present invention. In this non-limiting example, the prosthesis is a stent to be coated with a therapeutic agent. A first step 105 is to place the stent and the therapeutic agent container in the stent covering device. The system is then ready for stent processing. The system begins with step 110. A pre-coating procedure 115 collects information in the processing unit (not shown) of the stent coating device that will be used during a coating procedure 120. A post-coating procedure 125 verifies that the stent has been properly coated and approval must be given for its withdrawal 130.

The flow chart of fig. 7B illustrates the procedure for coating stents 140 known in the art. The user selects a pattern 145 according to the type of stent to be coated and the coating pattern to be delivered. The selected pattern varies depending on the parameters provided by the stent manufacturer and the coating to be applied. The procedure starts 150 according to the pattern that has been selected. The coating procedure 155 applies the coating to the stent and, when completed, the coated stent 160 is ready to be removed.

Fig. 8 illustrates the prescan procedure 115. The stent is prescan 205 prior to the coating procedure 120. At the same time, the application control module 200 is initialized. The initialization of the application control module comprises finding a specific point on the stent to begin the coating. The prescan is analyzed 210 in the processing unit. The analysis determines and compiles the coating coordinate table 215 to be used to position the application control module.

Often, there is a large deviation even between stents of the same design after the stent is pressed onto the balloon catheter. Press-fit does not always result in uniform deformation of the stent structure and, as a result, some portions of the stent may be more compressed than other portions. Some intersections of the stent struts may have different angles of incidence. The preprogrammed pattern is not useful for controlling these design deviations. Pre-scanning can provide a review of defects in the stent structure prior to coating and can also provide the best positions on which to spray the coating. Prescanning can also provide the path to be followed above the surface of the stent to be coated. In some applications, only a portion of the stent is to be coated and prescan can prevent excessive blasting of the coating at a specific location. If not, excessive jetting can result in the coating ending up on the balloon catheter.

Scanning can be accomplished by a variety of imaging techniques known in the imaging art, including, but not limited to, photographic, video, infrared, and VCSEL (Vertical Cavity Surface Emission Laser) technologies using various detectors. A VCSEL device can be used as the detector for optical imaging and can also act as the applicator itself. Choquette, Kent D., Vertical Cavity Surface Emitting Lasers- Light for Information Age, MRS Bulletin, p. 507-511, July 2002. In a non-limiting embodiment, a detector takes a photograph of the stent. The stent rotates slightly (for example, a half to a few degrees) and then another photograph is taken, resulting in at least several dozen photographs in all. The detector is focused close enough to the stent to register sufficient resolution relative to the coating droplet to be applied. If the stent is long, the rotation may have to be repeated to capture the top and bottom of the stent.

A light source can be placed on the same side as the detector or on the opposite side of the detector from the stent. In the embodiment where the light source is on the same side as the detector, the detector receives light reflected from the stent. The stent appears light in color and the balloon appears dark in color. In the embodiment where the light source is on the opposite side of the detector, the detector receives transmitted light through the balloon and around the struts of the stent. The stent appears dark in color and the balloon appears light in color. The contrast between light and dark color in both embodiments can be used for edge analysis. Edge analysis involves determining the edges of the stent and finding the centerline of the surface of the stent to be coated. The edges and center line determine the coating coordinates that are collected for each surface of the stent to be coated in the coating coordinate table.

In a non-limiting embodiment, the prescan is compared to a pattern index in the processing unit. This can be used to confirm the accuracy of edge analysis and provides a safe measure for detecting stent defects or edge analysis errors.

Overlay coordinates can be interpreted and encoded as raster type or data format vector. These data formats describe the different translation of the applicator by the Z unit. Both data formats comprise the use of an algorithm to find all the coordinates of the stent that should be coated and the compilation of a map of "points to be coated ”Or coordinates. Diagram 1 illustrates a coordinate map showing the location of a point on Z, R as a function of relative axial rotation R in degrees or radians.

ES 2 322 865 T3

Diagram 1

<img file="ES2322865T3_D0001.tif" />

The coatingVector involves considering the unique variables (for example, Z and R, rotation) and using another algorithm to select the shortest distance or, if not, the most efficient path to move between one coating coordinate and the next coordinate. closest to be coated. Vector overlay also involves creating a list of coordinates in sequential order. Table 1 illustrates a "best transform algorithm" as a coordinate table that correlates the location in Z with the angle of rotation R for each coordinate.

TABLE 1

<img file="ES2322865T3_D0002.tif" />

The processing unit control software can calculate a set of motion vectors for the application control module between each set of sequential coordinates. Vector parameters can comprise coordinates, Az (change in location between two adjacent points or coordinates on the Z axis), Arot (change in angle between coordinates), velocity between coordinates, and so on. Table 2 illustrates vectors that can be calculated from the table of coordinates in Table 1. Each vector can have a different velocity associated with it, represented as values ​​a, b, and c. Each vector can have a different quantity associated with it, represented as d, e, f, g, h values ​​that can be the same or different. Other parameters may also be associated with each vector.

ES 2 322 865 T3

TABLE 2

<td>Vector</td><td>Δζ</td><td>Arot</td><td>Speed</td><td>Quantity</td>

<td> 1-2</td><td> 3</td><td> 15</td><td>to</td><td>d</td>

<td> 2-3</td><td> 3</td><td> 15</td><td>to</td><td>and</td>

<td> 3-4</td><td> -3</td><td> 15</td><td>to</td><td>F</td>

<td> 4-5</td><td> 3</td><td> 0</td><td>b</td><td>g</td>

<td> 5-6</td><td> 6</td><td> 0</td><td>c</td><td>h</td>

A raster coating comprises the use of an algorithm to find all the coordinates of the stent to be coated and the compilation of a coordinate map. This is similar to the vector coating as illustrated in diagram 1 above. Hatching, however, also involves considering the unique variables (e.g. Z and R, rotation) and using a different algorithm to calculate and compile a table of Z-coordinate coordinates for each angle of rotation with predetermined rotation increments. . The term "rotation resolution" refers to the number of increments in the rotation angle. Screen-like coating is specific in terms of rotation resolution. This means that the raster impression is calculated and executed for a specific rotational resolution, or in a variety of other manipulations that interrelate the prosthetic article to be coated, the support for such prosthetic article and the applicator nozzle. Table 3 illustrates a coordinate table that maps the angle of rotation to the locations in Z. These locations: Z1, Z2, Z3, Z4, and so on. represent intersections with the surface of the stent to be coated for each angle of rotation.

TABLE 3

<img file="ES2322865T3_D0003.tif" />

The processing unit control software can calculate the Z coordinates for each angular position and direct the application control module and coating applicator to go to an angular rotation position and move along Z with a regulated, constant or variable speed. While moving along Z, the coating applicator injects into Z1, Z2, Z3, Z4, etc. After traveling the full length of the stent along Z, the application control module moves the coating applicator to the next angle of rotation and changes the direction along Z (now opposite to the previous direction), that goes through the coating applicator. While traveling this new direction, the coating applicator injects it into the following Z locations.

Additional frame-based manipulations may include, for example, rotational movements of the stent in conjunction with staggered series movements of the Z axis, or "screw-like" movements along a helical path of the stent achieved by the rotational movement and staggered movements of the stent. Simultaneous Z axis, as described later. In either case, the raster-based coating process results in movement relative to the stent and applicator that covers the entire prosthesis, while the vector-based coating process only traverses the "to be coated" surfaces. Therefore, the vector-based approach is object-dependent, while the frame-based approach is system-defined.

Fig. 11 illustrates a stent 2 on a balloon catheter 4. An axis of rotation 500 is also the axis of symmetry 500 of the stent. The enlarged inset of FIG. 11 shows the structure of the stent to be coated 505 and spaces in the stent structure where the balloon catheter 4 is not covered by the stent. During scanning, the stent rotates with incremental angles according to the rotation resolution to generate the coordinate table. During coating, the application control module rotates the stent at different incremental angles, generally smaller and therefore denser, and places the coating applicator at the Z, R locations to coat the stent. In a non-limiting embodiment, the coating applicator can drip-as-demand a coating with precision, as is known in the ink jet printing art.

ES 2 322 865 T3

The flow chart of fig. 9A illustrates one embodiment of coating method 120. The present embodiment contemplates raster coating performed by longitudinal movement of the applicator along the length of a cylindrical body and point-to-point ("PTP") rotation of the body. cylindrical or applicator around the circumference of the cylindrical body. An initial angle of rotation 300 is selected. The application control module moves the coating along the Z-axis 310, while controlling drip-on-demand at the Z coordinate 315, and receives the next coating coordinate from the processing unit 305. When the coating applicator has moved along the length of the stent, the application control module changes direction to move it along the Z axis of the coating applicator 320 and rotates the stent to the next angle of rotation. 325. This procedure is repeated by repeated steps 310-325 until the stent has been coated according to the coordinate table. In a non-limiting embodiment, the change in the incremental angle of rotation may be half a degree and up to 500 rotations of the stent may be required to cover each point in the coordinate table. Multiple coatings can be applied sequentially or simultaneously by repeating the steps and / or changing the deposit of the coating.

In another embodiment, weft coating can be performed by coating along the circumferential rotation of the barrel or applicator with a longitudinal PTP movement of the applicator along the length of the barrel. In another embodiment, the weft coating can be performed both by circumferential rotation of the cylindrical body or applicator and a longitudinal movement of the applicator with a longitudinal movement PTP of the applicator as well as by rotating the cylindrical body or the applicator along the circumference of the body. cylindrical. This embodiment results in a predetermined path of the spiral, helical or "screw" type.

In other embodiments, the raster coating can be performed following a predetermined path to apply coating material at desired locations on the prosthesis regardless of the coating pattern. In some embodiments, this predetermined trajectory may incorporate the overall contour or geometric shape of the prosthesis to effectively cover the surface area that includes the desired locations to be coated. In some certain embodiments, efficacy can be achieved using lines of symmetry or other geometric simplifications of the overall contour of the prosthesis.

The flow chart of fig. 9B illustrates coating procedure 155 that is known in the art. The coating nozzle is in an initial position 330. The controller receives coordinates of a pattern selected by the user 335. The controller interprets the coordinates in X, Y and a constant velocity movement Z 340 and positions the nozzle to squirt by controlling the delivery of the nozzle 350, the movement of the nozzle 355 and / or the movement of the stent 360. The nozzle then drips-as-demand 365. The nozzle then travels through the stent to the next coordinate based on the pattern selected by the user.

The flow chart of fig. 9C illustrates the coating procedure 155 which is known in the art and which also begins with the coating nozzle in an initial position 330. A photograph is taken of the nozzle, stent and / or coating 342. The photograph is analyzed using imaging software 345. The controller interprets the photograph and positions the nozzle to squirt by controlling the delivery of the nozzle 350, the movement of the nozzle 355 and / or the movement of the stent 360. The nozzle then drips-as-required 365. This requires formation of real-time imaging and adjustment prior to coating portions of the stent.

The flow chart of fig. 10 illustrates an embodiment of the present invention that includes a post-coating procedure 125. The coating applicator is held in standby mode 400, while the stent is post-scan 405. The scan analysis 410 analyzes the coated stent for errors on the coating and provides coating quality assurance and clearance 420. If the clearance is given, the stent coating is complete 130. In a non-limiting embodiment, the coating comprises pigment to facilitate analysis of the scan by differentiating between the stent and the coating. In a non-limiting embodiment, the post-scan images can be used to clear the stent. Post-scanning makes it easy to locate the coordinates where the coating was not applied due to jet problems. Post-scanning also makes it easier to locate leak points or "overspray" where the coating leaks from the stent to the balloon catheter.

The flow chart of fig. 12 illustrates an embodiment of raster overlay without prescan or postscan. The procedure for resurfacing a prosthesis 600 begins with the establishment 605 of the predetermined length L, the incremental linear movement Ax, and the incremental angular movement Δθ, along with a reference point recognized as a characteristic quality of the prosthesis. The detector is turned on 610 and the detector and applicator move 615 linearly from the reference point a distance Δχ and Δθ along L. The detector searches for targets 620 at desired locations on the prosthesis to be coated. If the detector finds a target, the applicator drips-per-requirements 625. If the detector does not find a target or after the applicator drips per-requirements 625, the detector and applicator move Δx 630. The detector determines whether it has traveled the full length L of the prosthesis 635 by determining whether the sum of the movements Δx is greater than or equal to the length L (ΣΔx&gt; L). If the detector has not traveled the full length L, then the detector and applicator move Δx 640 and search for a target 620. If the detector has traveled the full length L, then the detector and applicator move Δθ 645. The detector determines whether it has traveled the entire contour of the prosthesis 650 by determining whether the sum of the Δθ movements is greater than or equal to 360 degrees (ΣΔθ&gt; 360 °). If the detector has not traveled 360 degrees, then the detector and the

ES 2 322 865 T3 applicator moves 615 linearly a distance Ax and incremental Δθ along the length L. If the detector has traveled 360 degrees, then the coating has finished 655.

In another embodiment of the present invention, as shown in FIG. 14, a system 1400 includes a control system 1402 coupled to device 1 (see FIG. 1) that includes imaging system 32 and coating application control module 36, previously described. In addition, the control system 1402 is coupled to a user interface 1406 to allow the user to enter user-selectable attributes of the system, for example, material type, droplet size, droplet rate, total volume. to be deposited, etc., in addition to being able to monitor the operation of the system and receive alerts indicating how the system is working. User interface 1406 may present this information via a display device such as a computer monitor and may use a graphical user interface as is known in the art.

Device 1 is coupled to control system 1402 and incorporates the drip-on-demand applicator described above to place the coating on the medical device. Device 1, in one embodiment of the present invention, is sized to fit on a desk.

The control system 1402, in one embodiment of the present invention, is a personal computer or ordinary computing device that implements one or more application programs to control and interact with the imaging system 32, the user interface 1406, and the application control module 36. The computer can have an operating system as it is known, such as Microsoft Windows, UNIX, Linux or AppleOS. The application programs can be a combination of commercially available programs or programs written in any one of several available programming languages ​​including, but not limited to, C, C ++, Java, Perl, and Fortran.

The computer, as before, can be any one of several devices, however, these devices have some components and / or functionalities in common, regardless of their relative technical complexities. As shown in fig. 15, a computing device includes a central processing unit 1500, a memory 1502, an input / output device 1504, for example a keyboard, an auxiliary keyboard or a touch screen, storage 1506, for example a hard disk drive and an interface 1508 for communication with a network. A bus 1510 couples these devices together to allow communication between them. As described above, the coating device 1 can be sized to fit on a laboratory desk or table in a clean room or suitably sterile environment. As shown in fig. 16, the control system 1402 would be coupled to the coating applicator 1408.

Another embodiment of the present invention includes a method 1700 for capturing and processing information regarding a device, eg, a stent, to be coated, as shown in FIG. 17.

In the following description, a stent is referred to as the medical device on which the coating is placed. It should be understood, however, that the present invention is equally applicable to any number of medical devices on which a medicinal coating is desired. Although the description refers to a stent, for the sake of clarity only, the present invention is not limited to just coating stents.

The stent is placed within the field of view of the imaging system and scanned to obtain several images covering the entire target surface, step 1702. The image obtained is stored as digital information either in memory or on a medium. adequate storage. As part of the procedure, the image is converted into digital information to obtain a digital representation, step 1704. This digital representation may include, but is not limited to: generating an image to visualize the stent and the structure on which it is mounted, as shown, for example, in FIG. 18. It is not necessary, however, for an image to be displayed for an operator to view. It should be noted that the image shown in fig. 18 is one of many that could be generated. The digital information is then processed to differentiate the digital information that represents the stent from the digital information that represents the portion of the scan that is not part of the stent, step 1706.

When the stent information or data has been differentiated from the non-stent data, the locations or coordinates where the coating material will be placed are determined, step 1708. Up to this point in the procedure, the representation of the stent has been determined. maintained in the virtual or digital domain. That is, the representation of the stent and thus the coordinates of the coating are represented as locations in the digital representation. Thus, in step 1710, these digital coordinates representing where the coating material is to be placed are translated into physical coordinates representing physical locations on the stent for deposition of the coating material. These physical, or actual, coordinates representing locations on the stent are used by the control system 1402 to actuate the coating application module 36 to apply drops of coating material only to the desired locations, step 1712.

They will now be described in more detail with respect to the flow chart and fig. 19 details of the procedure generally described above with respect to fig. 17.

Multiple images of the stent are collected by rotating the stent around its axis, stopping the stent, capturing the image, and then rotating it in increments until a full rotation has been achieved, step 1902. In a

For example, the stent rotates 15 ° for each image that is captured. The choice of increment is not intended to be a limitation of the present invention and any suitable increment is anticipated for multiple imaging around the circumference of the device. As shown in fig. 19A, multiple images of the stent, represented in cCd pixels, are obtained for each rotated section. At step 1904, the stent is positioned in each of the images. This involves processing the image data to distinguish the stent from any background. In addition, the axis of the stent is calculated in each image to measure rotational eccentricity, which will be further analyzed later.

The central segment of the stent is removed around the axis of each image. In one embodiment, the bottom may be a balloon catheter on which the stent is mounted or a mandrel configured to removably receive the stent. In this case, where a CCD imaging device has been used, the pixels of the CCD representing the stent are placed. Consequently, all images are binary coded because the pixels of the CCD representing the stent have been given a different value than the pixels of the CCD that do not represent the stent, step 1906 and fig. 19B. The multiple images of the stent that have been captured and binary encoded are then combined to obtain an image of the stent, step 1908, fig. 19C. The combination is performed, in one embodiment, according to the stent boundary locations in the different images. Although the boundaries do not appear on the combined image, they serve as indicators of relative position, since an expected diameter of the stent is already known. Furthermore, any pixel that is identified as part of the stent will also be identified in the combined image.

When the images are combined to obtain a complete image of the stent, either edge detection or skeletal detection of the combined image is performed, step 1910. In skeletal detection, a midline of a stent strut is identified processing the combined image of the stent. There are various algorithms known to those skilled in the art for the identification of midpoints of structures represented by digitized information.

Alternatively, the edges of a strut of the stent can be detected. As is known, a stent strut includes an external surface and an internal surface, in which the external surface would be in contact with the wall of the vessel in which the stent is to be placed. Conversely, an internal surface of the stent would be in contact with luminal flux, eg, blood, in a blood vessel. Each strut of the stent therefore includes lateral surfaces that join the inner and outer surfaces. It is the edge points at the transition from an external surface to an edge that are detected.

The images shown in figs. 22A-22C represent data from a scanned stent that has been binary coded such that the white portion of the image represents the stent and the black portion represents non-stent areas (Fig. 22A; the results after the stent has been completed). performed a midline determination (Fig. 22B), where the white portion represents the midline, and a representation of the edges that have been detected, where, as before, the white represents the location of the edge pixels in the image (Fig. 22C). As is known in the art, any one or more of the Zhang and Suen thinning algorithms, the Stentiford pre-processing algorithm, or the Holt post-processing algorithm can be used.

A droplet map is then generated that identifies where discrete drops of coating material are to be placed, step 1912. In one embodiment of the present invention, the droplets are placed along the midline of the stent strut, as shown. identified by skeletal detection in step 1910. Alternatively, drops of coating material are placed along the identified edge locations of the stent strut. A general representation of skeleton placement and edge placement is shown in fig. 19E. Of course, one skilled in the art would understand that the present inventors envision that the coordinates of the coating could include portions of the stent in which the coating is placed only along the edge, or only in the midline, or in a combination of edge and midline, or having portions of the stent where no coating is to be placed.

Proper placement of the liner material at the edge of the stent strut facilitates placement of the liner on the lateral surfaces of the stent strut. Selection of the characteristics of the coating material including, but not limited to, viscosity, density, temperature, speed, etc., allows coating of the stent on the outer surface and the side surface without coating the inner surface. Placing the coating on the sides of the struts makes it possible to deliver more medication to the patient. In some cases, however, it has been found that the deposition of coating material on an internal surface, especially if a stent is mounted on a balloon catheter, can interfere with the release of the stent from the balloon surface due to adhesion. of the coating. Also, in some applications, the internal surfaces of the stent are coated. According to one embodiment of the present invention, the coating with specific characteristics such as viscosity and temperature located on the sides of the strut will spread and converge on the interior surfaces.

The stent edge locations, from the image data, represent the optically or visually detected edge, that is, that point or those points that represent a boundary of the stent. These edge locations or coordinates, as above, can be used as the actual locations of the drops. In an alternative embodiment, these edge locations or coordinates are used as reference locations from which the drops can either be shifted inward, here defined as toward the median axis, or shifted outward, that is, away from the axis. medium, depending on the desired characteristics of the coating. The magnitude and direction of any displacement can be changed based on the local geometry of the stent where, for example, curvature or shape can dictate the direction or magnitude of the displacement.

ES 2 322 865 T3

As discussed above, in step 1914, the droplet coordinates in the droplet map generated in step 1912 are translated from pixels with, for example, X, Y coordinates, to jet height and stent angle Z, R , stage 1914. In this embodiment, the physical coordinates for the locations where the coating material drops are to be placed are expressed as a Z, R pair, where the Z coordinate, which could be measured in microns, represents a point along of a longitudinal length of the stent, where a location known as the origin has been chosen, and the R coordinate represents, in radians or degrees, a specific angular location around the circumference of the stent, again where an angular origin has been defined, fig. 19F.

According to the present invention, there are two examples of coating paths: a linear path and a helical path. Each of these will be described in more detail below.

As described above, a path that the coating applicator traces on the stent surface is independent of the coating pattern and stent topology. In one embodiment, the coating applicator follows a linear path, substantially parallel to the longitudinal axis of the stent, through the surface of the stent. When the coating applicator, following this linear path, intersects a coordinate of the injection map or drop map, then a drop of coating material is placed on the stent. In step 1916, the coating coordinates generated in step 1914 are placed in a sequence to facilitate placement of the coating material when the applicator is moved in a raster-based or linear motion through the stent. In the linear or raster example, the injection map is scanned vertically to create a raster of vertical cover paths. An angular difference between adjacent vertical paths defines the angular resolution of the coating. This angular difference has a limit due to the difference between the injection times of two drops at the same height Z, in adjacent paths. This time difference is chosen to be greater than a certain value to prevent the coating from dripping while it is drying.

An alternative embodiment of the present invention, with respect to the example of a coating with a linear path, maintains the angular resolution to prevent the coating from dripping by introducing a phase difference, which is called linear phase shift.

In linear phase shift an angular difference is established, around the circumference of the stent, between adjacent vertical paths to a value that prevents the coating from dripping by adjacent drops of material. As a result, the coating resolution is improved by repeating the coating with raster paths several times across the surface of the stent, each time with a slightly different phase.

As a non-limiting example, if an angular difference between adjacent raster scans is 1 °, that same scan can be repeated four times with a phase shift of G °, creating four different raster scans with an overall angular resolution of G °. . As a non-limiting example, starting at an origin angular location, 0 °, the applicator moves along the length of the stent from one end to the other depositing material at locations as defined on the injection map, the stent then rotates until the 1 ° location, then a scan back for deposition is performed and this is repeated around the stent until 0 ° again. The stent is then rotated to position the applicator at the G ° location, a linear scan is performed, the stent is then rotated to 1G °, scan, etc. around the circumference in steps of 1 ° and back to where it started, that is, G °. This is repeated starting at G °, around in 1 ° increments, and then in% ° and around. Therefore, although the angular resolution increases, due to the phase shift, there is no degradation of drops in the same Z in adjacent scans due to the time between depositions.

If more than one application stream is used in step 1918, the paths are divided so that the coordinates falling within each application stream are assigned correspondingly.

In another embodiment, referring to FIG. 20, one or more injection heads of the coating applicator trace a helical path 2000. The helical path 2000 may be the result of a linear movement of the coating applicator substantially parallel to the longitudinal axis of the stent in combination with the rotation of the stent about its axis. The jet path generated in step 1916 for a relative helical movement of the coating applicator over the stent would be configured to allow operation of the applicator when the coating applicator is located on a coordinate where a drop of coating is to be deposited. coating material.

In one embodiment of the present invention, with respect to helical deposition of coating material, multiple helical paths can be defined, offset by a known phase from each other, to lay the discrete drops of coating material, as shown schematically in FIG. twenty-one. By using offset helical paths to deposit droplets of coating material on the surface of a stent, the droplets can be positioned closer to each other and more precisely by multiple helical passes. With this procedure, similar to the phase-shifted linear approach above, the material drops that have already been deposited are sufficiently dry so that subsequent drops can be brought much closer together or even overlapped without displacing the material already placed. The number of helical passes and therefore the phase difference between them can be chosen by the user to define the coating passes. The coating coordinates are then arranged in a sequence that will contain the helical deposition.

ES 2 322 865 T3

In the helical example, the injection map is scanned diagonally to create a helical coating path. As before, the helical path can be the result of the rotation of the stent at the same time as the linear movement of the coating applicator. A vertical step for one turn of the propeller path defines a vertical resolution of the coating. This vertical pitch has a lower limit due to the difference between the injection times of two drops with the same angle, in successive turns of the propeller. Again, this time difference must be greater than a certain value to avoid dripping. In order to maintain a sufficiently high vertical resolution, and to keep the vertical pitch of the helix above the limit, one embodiment of the present invention addresses helical phase shift.

In helical phase shift, the vertical pitch of the helix is ​​kept high enough to prevent the coating from being removed. Coating resolution is optimized by repeating the helix several times, each time starting at a different angle phase. As a non-limiting example, if the vertical pitch of the helix is ​​40 microns, it can be repeated four times with a phase shift of 90 ° at the helix start point, creating four different helical paths with an overall vertical resolution of ten microns.

To facilitate multiple layers of coating material, multiple full passes can be programmed over the device and the coating applicator will complete that number of multiple passes. Alternatively, when the cover layers are of different materials, a first injection map can be generated for one material and a second injection map can be generated for the next layer. The same points do not need to be chosen on each layer. According to one aspect of the present invention, ink jet applicators can be dedicated to specific materials and connected or disconnected according to coating requirements.

In another embodiment of the present invention, geometric features of a stent topology are detected and identified. Once detected and identified, the locations of these geometric attributes are obtained, that is, the locations of the CCD pixels and the corresponding physical locations. The characteristics of the coating material to be placed at these identified geometric locations are adjusted accordingly.

In a non-limiting example, where it is known that a large amount of stress can be placed on the stent, by, for example, expansion, then more or less of the covering material can be deposited at that location. In one embodiment, a filtering operation is performed to remove or add coating spots on a specific area of ​​the stent. In addition, for example, at the distal and proximal ends of the stent where it is most likely to cause irritation of the vessel in which the stent is placed, a different formulation of the covering material can be placed. In accordance with the present invention, any number of different characteristics of the covering material can be adjusted depending on the detected geometric characteristic of the stent, including, but not limited to, changing the droplet size, changing the composition of the material, deposition of more than one drop of a material at each location in the area, adjust the temperature of the material to be placed, adjust the density per unit area of ​​the drops in that area, lay multiple layers of material, etc.

Upon detection and identification of a local geometric characteristic of the stent, according to an embodiment of the present invention, any one or more of: a thickness of a coating, a number of layers of a coating and the choice of coating material can be adjusted . Furthermore, the areas to be masked, ie an area in which no coating material will be deposited, can also be determined. In the case of masking, no cover points will be defined for one or more portions of the stent or medical device.

According to a method 2300 of this aspect of the present invention, at step 2302, as shown in FIG. 23, rules are established for specific geometric characteristics. These rules can be obtained by empirical observation or from real measurements. In step 2304, the geometric features are identified, for example, a U-shape, an S-shape, a T-joint, or an X-joint, as shown in FIGS. 24A and 24B. In step 2306, as before, the characteristics of the drops can be adjusted for the areas of the selected geometric characteristics.

As a non-limiting example, a decrease in the density of the coating material near U-shaped struts has been determined to be beneficial. A parameter can be selected by the user to be adjusted for a curvature factor of the U-shape and its degree of influence, that is, how far from the U-shape the coating density should be adjusted. In addition, a decrease in the density of the coating material near an X-joint or a T-joint provides better coating performance on the stent.

Although representative examples of geometric configurations have been identified, the present invention is not limited to just these shapes or attachments. Any identifiable geometry that ensures an adjustment of coating parameters is encompassed by the present invention.

In an alternative configuration, a user, eg, a physician, prior to a procedure, can identify portions of the stent to which the parameters of the covering material are adjusted. As an exemplary embodiment of the present invention, a representation of the scanned stent may be displayed on a display screen. Using a user interface, perhaps a touch screen or a stylus or similar indicating device, the physician identifies areas of the stent and characteristics of the stent. In one example, the physician may choose a medicinal coating of a certain type for placement on an intermediate portion of the stent and a different material on the proximal and distal portions. Any one or more of several parameters could be adjusted or chosen by the

ES 2 322 865 T3, including, but not limited to, the drug, the density per unit area, the number of layers of the coating material, and a temperature at which the coating will be ejected. Furthermore, global parameters could be selected, for example: sections of the stent could be selected in which the coating is placed on the midline of the stent but other sections the coating is placed on the edges. The amount and direction for edge coating displacement can also be selected on a global basis, ie, either for the entire stent or for portions thereof.

When the parameters have been chosen and established by the physician, the present invention will convert the information on the jet map to control the ink jet applicator. In an alternative embodiment, the clinician may be able to select either a helical or raster application or, depending on the parameters that were set, the system may allow some parameters to be user selectable but not others.

Additionally, predefined coating patterns can be created to use as a template for stent coating. When, for example, a clinician has had repeated success with a particular veneering model, it could be repeated on subsequent stents. The system, while scanning each stent individually, would then apply the coating parameters and generate the injection map, that is, the coordinates where the coating material is correspondingly deposited. What's more, a stent can be coated by a prescription issued by the doctor to a pharmacy with a stent coating system.

As a relatively simple example, a physician may determine that stents having a density A of material B in the central third of the device and a density C in the remaining proximal and distal portions provide beneficial results. You could then enter these general requirements and the system of the present invention would identify the stent coordinates found within the portions, define the injection map, and then coat the stent accordingly.

A calibration procedure is performed on the system to ensure accurate conversion of the CCD pixels into the physical coordinates of the stent or device to be coated. According to a calibration procedure 2500 depicted in FIG. 25, a predefined pattern of dots is injected into a calibration target, step 2502, using an injection material visible to the camera. These points are injected into locations known as Z, R coordinates, that is, angular position around the target and linear position along its length, as described above. Images of these points are collected, step 2504, from several different angles around the device. The choice of the number of different angles is not limiting as long as a sufficient number is chosen to obtain the necessary calibration points. The positions of the drops on the calibration target are determined, step 2506, and the positions in the images are detected, step 2508. A transformation of the image pixels at the known physical locations is then calculated, step 2510. Since it is known where the drops were intended to be located and where the drop positions have been detected, a least squares fitting procedure is performed and the transformation calibration data or parameters are calculated and stored, step 2512.

As shown in fig. 25, in an embodiment of the present invention, a mapping table is maintained for the system that associates one or more pixels with respective X, Y coordinates with a location on the stent with Z, R coordinates. Alternatively, if the adjustment or calibration determine that the behavior of the system can be expressed as a function or formula, then the formula would be stored and a correspondence table would not be used. As one skilled in the art knows, the calibration procedure can be performed according to a periodic schedule to take into account any variations in the system that may occur.

In embodiments of the present invention, both a "bare" stent and a stent that is mounted on a balloon catheter can be coated. In the case of a bare stent, it is mounted directly on a mandrel to position it within the system. In a system that operates with the stent mounted on the mandrel, all the components rotate concentrically around the same axis, that is, the stent rotates around the axis of the system.

The same concentric rotation may not be present with a stent mounted on a balloon catheter. As described above, a stent mounted on a balloon catheter can be "off-center" from a longitudinal axis of the balloon catheter due to the pressure fixation procedure. The pressure fixation process is not so exact that the stent is mounted on the balloon so that the stent and the guidewire lumen of the balloon catheter are concentric. Often there is an eccentricity that is introduced by the press fit procedure.

In one embodiment of the present invention, the balloon catheter would be mounted on a relatively rigid wire threaded through the guidewire lumen of the balloon catheter, i.e., a mandrel. Although this mandrel is configured to rotate about the central axis of the system, the compensation for rotational eccentricity of the stent with respect to the mandrel and therefore the system has to be calculated.

Compensation for rotational eccentricity will be described with reference to FIG. 26, which is a cross section of the stent, at a Z location along its length, mounted on a balloon catheter that is mounted on a mandrel. A surface 2602 of the stent rotates about a central axis 2604 of the stent. A central axis 2606 of the system is defined by the mandrel of the system and an orbit 2608 of the injection surface represents the orbit around the stent in which the applicator can move. As before, the applicator rotates about the center axis 2606 of the

ES 2 322 865 T3 system in the orbit 2608 of the injection surface. It should be noted that the depiction of the rotating applicator can be done either by rotating the stent with the stationary applicator or by moving the applicator around the stent or a combination of these movements. The description herein is intended to describe the compensation procedure and not to limit any of the embodiments of the present invention.

The surface 2602 of the stent is the actual surface of the stent and, as before, is not necessarily centered in the center 2606 of the system. The central axis 2604 of the stent may also be at a different point at different Z locations along the length of the stent. The location of the stent axis is located in each of the 2610.1-2610.5 images. As a representative example, referring to image 2610.2, the center axis 2606 of the system is located in the center of image 2610.2, as would be expected because the imaging system is concentric with the center axis 2606 of the system and is represented by a broken line 2612.2. The location of the stent center axis in image 2612.2 is determined by detecting the stent boundary in the image and finding the center of that detected boundary. As shown in fig. 26, the central axis of image 2612.2 is located along dotted line 2614.2. By performing this procedure, the location of the stent axis is calculated as a function of Z.

The central section of the stent (dotted lines) is detected in each image 2610. As previously described, the central segments are combined to create the image of the stent surface. The image of the combined stent surface is processed to extract the injection sites and converted from the CCD coordinate system to the stent coordinate system.

The present invention teaches a method for coating a prosthesis as well as a kit for coating a prosthesis, a system for coating a prosthesis, and an application control module for coating a prosthesis.

Embodiments of the above-described invention can be implemented in either all software, all hardware, or a combination of hardware and software, including program code stored in a firmware format to support dedicated hardware. A software implementation of the above-described embodiment (s) may comprise a series of computer instructions securely affixed to a tangible medium, such as a computer-readable medium, for example, a floppy disk, CD-ROM. , ROM, or fixed disk or transmissible to a computer system on a carrier wave, via modem or other interface device. The medium can be either a tangible medium, including, but not limited to, optical or analog communication lines, or it can be implemented with wireless techniques, including, but not limited to, microwave, infrared, or other transmission techniques. The series of computer instructions both contained in a tangible medium and in a carrier wave incorporates all or part of the functionality previously described herein with respect to the invention. Those skilled in the art will realize that such computer instructions may be written in various programming languages ​​for use in many computer operating systems or architectures and may exist in executable form. In addition, such instructions may be stored using any memory technology, present or future, including, but not limited to, semiconductor, magnetic, optical, or other memory devices, or may be transmitted using any communication technology, present or future, including , but not limited to, optical, infrared, microwave or other transmission technologies. It is contemplated that such a computer program product may be distributed as removable media with attached printed or electronic documentation, eg, shrink wrapped software, preloaded with a computer system, eg, on system ROM or fixed disk. , or distributed from a server on a networked computing platform, for example, the Internet or the World Wide Web.

Furthermore, with respect to the control system 1402, it is envisioned that the control system 1402 could be implemented as a computer connected via a network to the applicator device 1. Although the user can access the functions through a local terminal, the processing can be done remotely. Of course, someone skilled in the art would understand the technical requirements for such a network to function properly.

What is more, the applicator device 1 may be located remote from the user and the parameters for the coating are transmitted to a central facility where the device 1 is located. As an example, a hospital may have a stent coating facility located centrally within the same building where the procedure is performed on the patient or close to it. The physician / user may be able to enter the necessary parameters via a terminal or interface and then the coating is applied, the stent is delivered to the physician for insertion, and the stent is inserted into a patient. This is similar to a “just-in-time” manufacturing procedure where components are ordered / created shortly before they are needed.