Seite/Page: 1 Just where it s needed Continuing miniaturisation of many products requires a method of dispensing very small amounts of liquids Inkjet technology is capable of applying adhesives and many other functional liquids as well as inks with great precision Its versatility and potential in industrial applications is illustrated by the example of coating a drug-eluting stent with a polymer/drug formulation Precision coating of medical devices achieved by printing Wilhelm Meyer* In many production processes it is necessary to dispense small amounts of fluids There are many possible examples: placement of adhesives to bond devices such as optical lenses or fibres, printing of functional materials onto computer displays or sensors and dosing of lubricants as well as the application of coating materials A consequence of continuing miniaturisation is that the amounts of fluids also need to be "miniaturised" Conventional methods for dispensing and dosing are at their limits The volumes achievable are too large for applications in the millimetre and sub-millimetre range Optical fibre systems require precision bonding An example which illustrates this problem is shown in Figure 1; the bonding process for an optical fibre coupling device with a laser diode A small lens system needs to be integrated in order to couple the energy of the laser source to an optical glass fibre The parts are only a few millimetres in size and the lenses need to be placed very accurately to obtain high efficiency coupling of the laser energyin a final step the lenses are fixed by application of an optical adhesive If a conventional adhesive dispenser is used, a droplet the same size as the whole device is placed in it The adhesive material floods the whole assembly It cannot be guaranteed that the gaps, which have a width of approximately 100 µm, are properly filled The large amount of material can also jeopardise the precise positioning of the lenses because they float inside the large adhesive drop What would be a better way to fill only the gaps between the lenses? The method of choice is the use of smaller amounts or droplets of adhesive deposited successively into the gap without touching the parts The advantage is that smaller droplets can be placed more precisely into a gap because the drop size can be smaller than the width of the gap The controlled material flow allows the adhesive to spread through the entire gap by capillary forces The latter is very important for the quality of energy coupling In addition, the whole amount of adhesive is controlled very precisely by counting the number of droplets put into the gaps A method for the generation and contactless application of small droplets is already well-known For more than 20 years inkjet technology has been used for placing (or better printing) small droplets onto paper for producing letters, pictures and other media As shown in the example above, this technology is also useful for quite different applications Today, inkjet technology is already well on the way to becoming a versatile tool in numerous industrial applications Practical issues can be complex and varied The inkjet concept is simple but its realisation can be complex Because of the small volume and relatively large surface area, material properties such as surface tension and viscosity have a large effect on the generation of drops If water drips out of a small capillary, a hanging droplet is built due to the surface tension The drop grows so long as its gravitational force is smaller than the force due to surface tension If the gravitational force becomes greater, the drops falls off This example shows that a relatively high force, much higher than the gravitational force, is needed to generate small free-flying droplets In inkjet technology the force is generated by a very brief but high acceleration Within microseconds a small amount of liquid is accelerated through a nozzle, building a small jet When the acceleration decreases the jet is disrupted due to its inertia and a small droplet is formed To develop new processes with inkjet technology, the materials and their resultant interactions have to be considered Beyond surface tension and viscosity, many other properties have a significant impact on the end result The main properties and interactions are shown in Figure 2 Most important for drop generation is the composition of the material and its resulting rheology Typically, polymers do not have a Newtonian viscosity, which means their viscosity changes with the acceleration and speed with which these materials are moved Because of the high acceleration and shear rate inside an inkjet dispenser, the drop generation of materials such as dissolved polymers is not guaranteed or may differ very much with concentration and different solvents The nozzle configuration and other settings of the dispenser also affect the results When the material hits the substrate, once again viscosity and surface tension, along with evaporation and material adhesion, are important factors which determine the shape of a droplet or a line structure To develop a stable and reliable inkjet process, especially with fluids for industrial applications, much skill and experience is needed Stent coating provides efficient drug delivery Inkjet technology allows the precise application of material on small structures in the sub-millimetre range The advantage is that droplets can be placed individually By means of this contactless drop-on-demand technology, small structures can be coated with different materials A good demonstration of the versatility of such a method is the process of coating surgical stents Stents are mainly inserted into blood vessels to prevent flow constrictions Typically, coronary stents are implanted after the reopening of coronary arteries to prevent the collapse of the soft arterial wall after treatment Such a stent consists of a mesh or scaffold made of metal Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 2 The design of the scaffold allows stents to be crimped onto a balloon catheter After insertion of the catheter into an artery, its balloon is pumped up This forces the scaffold to expand The expanded structure supports the blood wall To prevent so-called restenosis by unwanted cell growth a so-called drug eluting stent is inserted This stent type is typically coated with a mixture of two different materials, the drug which prevents the cell growth and a polymer The polymer acts as a drug delivery reservoir When the stent is inserted into the arteries the drug is delivered to the surrounding material inside the blood vessel To prevent a large amount of the toxic drug being released into the blood circulation, the coating needs to be located only on the outer surface of the stent which is in direct contact with the artery wall Flexibility of stent poses practical problems To coat drug eluting stents, a very selective process such as inkjet printing is needed to place the coating material Such a stent is typically a few millimetres in diameter and some 10 millimetres in length The scaffold consists of a fragile structure of struts with a thickness and a width of about 100 micrometres (see Figure 3) Due to its small dimensions the stent is very flexible This means that a flexible device with a complex structure needs to be coated with a mixture of polymer and drug The coating material contains a medication, its amount of coating has to be controlled very precisely Because the mass of coating material on each stent can be very well controlled by counting the number of droplets deposited, inkjet technology is an excellent choice After the optimal inkjet configuration and parameter settings for drop generation of the coating material are developed, the mechanical properties of the stent have to be considered for further process development As already described, the scaffold is very flexible and therefore not easy to handle The stent therefore needs a mechanical support and fixture during the coating process To obtain a stiff configuration, the tubular stent is moved on a mandrel, introducing another type of problem After the stent is moved onto the mandrel the final location of its assembly of struts is neither controlled nor at all predictable The strut elements are shifted relative to each other during the movement of the stent onto the mandrel Consequently the variation of the strut structure from stent to stent is not reproducible and to place the droplets each strut element needs to be localised individually Therefore no master curve can be built in, and each stent on a mandrel needs to be mapped individually during the coating process The information about strut location is transformed into coordinates where the drops need to be deposited Finally the computational system provides an electrical signal to trigger the inkjet dispenser and shoot droplets of the coating material at the right location when the strut element is underneath the dispenser outlet By repeating this process drop by drop along the helical movement, the stent is completely coated The aim is to obtain a homogeneous coating with a material coverage of almost a hundred percent To achieve such high quality, additional algorithms are implemented in the computational system These algorithms incorporate the different pattern of the strut elements at different locations; e g knots, crossings or changes of width along the strut structure Depending on the material used, high quality coatings with thicknesses in the µm range can be obtained (see Figure 5) To increase the amount of drug material on a stent the coating process can be repeated a few times Results at a glance» The ongoing miniaturisation of many products requires a technology capable of dispensing small amounts of liquids Small volumes down to a few hundred picolitres need to be placed very precisely in volume and location» One of the most technically versatile ways to meet these requirements is inkjet technology, which is already used in medical applications for coating implants, as well as for dispensing small amounts of adhesives» The limitations and advantages of this technology are reviewed Coating of a drug diluting stent is given as an example of the versatility and potential of inkjet technology in complex industrial applications Precise control over the coating can be achieved, even though no two units have exactly the same configuration, by using real-time computer control * Corresponding Author: Wilhelm Meyer Microdrop Technologies GmbH Tel +49 40 53 53 830 wilhelmmeyer@microdropde Real-time computer control is essential The technical solution is shown in Figure 4 The mandrel with stent is fixed on a rotational system At the right hand side an optical scanning device is fitted A microdrop inkjet dispenser is fitted vertically to the mandrel The nozzle outlet of the inkjet dispenser is aligned with the rotational axis of the mandrel During the coating process the mandrel is rotated and the inkjet dispenser is moved parallel to the rotational axis These combined movements result in a helix-shaped trajectory around the stent During this movement the stent is scanned and by means of a computational system the actual location of each strut is defined Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 3 Figure 1: Bonding process in a laser coupling device for optical fibre systems: (a) overview of laser coupling device; (b + c) adhesive dispensing with macroscopic droplets; (d) smaller droplets improve the dispensing process Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 4 Figure 2: Drop generation and impact during inkjet dispensing process are influenced by material properties and other effects Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 5 Figure 3: Drug diluting stent; only the outer surface needs to be coated (see enlarged view) Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 6 Figure 4: Design of the stent coating process Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 7 Figure 5: Stent coating in progress showing inkjet dispenser and rotating mandrel (left) with a close-up view in which the inkjet droplets on the stent are dyed to assist in visualisation (right) Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000
Seite/Page: 8 Figure 5: Stent coating in progress showing inkjet dispenser and rotating mandrel (left) with a close-up view in which the inkjet droplets on the stent are dyed to assist in visualisation (right) Vincentz Network +++ Plathnerstr 4c +++ D-30175 Hannover +++ Tel:+49(511)9910-000