FIELD OF THE INVENTION

The present invention relates to method and apparatus for applying a material to the surface of a polymer article during its production.

BACKGROUND OF THE INVENTION

In biotechnological and medical applications, it is desirable to apply functional coatings, e.g. proteins, to defined areas of articles for use in laboratories or as medical devices. A method of producing such articles without substantially affecting the functional coating would be desirable, in particular if such articles can be mass produced at a relative low price as many of these articles must be disposable.

WO 2006/097483 discloses a method of providing at least one heat sensitive material on at least part of the surface of a polymer article formed from a heated polymer whose temperature is sufficient to adversely affect the at least one heat sensitive material.

The present invention is a further development of the said publication allowing for an improved method for providing a heat sensitive material, such as a

biomaterial, on at least part of the surface of the polymer article without adversely affecting the heat sensitive material.

One problem encountered in transferring heat sensitive materials, such as biomaterials, from a shaping surface to a polymer article is that transferral may be partial or not complete.

Hence, an improved method for producing a polymer article comprising at least one heat sensitive material, such as biomaterial, provided onto at least part its surface would be advantageous, and in particular a more efficient and/or reliable method for producing a polymer container would be advantageous. OBJECT OF THE INVENTION

It may be seen as an object of the present invention to provide an improved method for producing a polymer article that solves the above mentioned problems.

It is a further object of the present invention to provide an alternative to the prior art.

SUMMARY OF THE INVENTION

The invention relates to a method for transferring thin layer of a material, such as a biomaterial, with a thickness value relevant to a monolayer of proteins, from a shaping surface to a polymer article by forming the polymer article, the method comprising : applying at least one thin layer of a material onto at least one part of a shaping surface having a plane or at least partially textured primary form previously treated to achieve a topographical clearness and bringing a melted polymer in contact with the shaping surface to form the polymer article.

Generally, perfect transferral of very thin layer of material, e.g. having thickness within a range relevant to a monolayer of proteins, i.e. less than 100 A, more preferably less than 50 A, and even more preferably less than 10 A. By applying the method of the invention transferral of very thin layers of material is possible with a higher degree of precision which cannot be reached by other methods. By treating the shaping surface to achieve a topographical clearness, i.e. treated to achieve a surface roughness of less than 300nm, more preferably less than 200 nm, even more preferably between 100 nm and 0 nm, the transferral between the shaping surface and the polymer article is improved as the coverage by the thin layer of material onto the shaping surface is improved.

The previously described object and several other objects are intended to be obtained in a first aspect of the invention by providing a method for producing a polymer article comprising at least one heat sensitive material provided onto at least part of its surface, the polymer article formed from a polymer heated at a temperature sufficient to adversely affect the at least one heat sensitive material, the method comprising : applying at least one heat sensitive material onto at least one part of a shaping surface having a plane or at least partially textured primary form previously treated to achieve a topographical clearness, the shaping surface being at a temperature at which the heat sensitive material is not adversely affected, and bringing the heated polymer in contact with the shaping surface to form the polymer article, while maintaining the shaping surface at a temperature at which the heat sensitive material is not adversely affected, thereby transferring at least one heat sensitive material from the shaping surface to the polymer article surface.

Heated polymer is used herein to identify a polymer which have been subjected to a raise in temperature so as to soften and/or melt its structure accordingly to the method of production used, e.g. injection molding or calendaring.

The method has the ultimate advantage of improving the quality of the surface coverage of the polymer articles on which the shaping surface transfers the heat sensitive material. Generally applying a thin layer of heat sensitive material onto a shaping surface may produce an incomplete coverage due to poor surface properties of the shaping surface properties, e.g. high surface roughness. When a shaping surface has a high surface roughness application of thin film of heat sensitive material may produce partial and not homogeneous deposition as the high roughness produces valley and ridges which may experience different thicknesses in deposition. In turn shaping surfaces with a high surface roughness provide a partial, not homogeneous and incomplete transferral of the heat sensitive material to the polymer article.

Even when shaping surfaces are provided with a degree of smoothness within the optical clearness, transferral to polymer article may be not complete. Optical clearness for a shaping surface is herein defined as having a surface roughness not lower than 1 μηη.

By employing a shaping surface with a topographical clearness, the quality of the application of the heat sensitive material to the polymer article is greatly improved. By bringing a heated polymer, i.e. soften and/or melted, in contact with the shaping surface to form the polymer article the thin layer of material, e.g. biomolecules, are transferred at least partially to the polymer article producing a thin layer of material, e.g. biomolecules, of high quality.

The trasferral of the thin layer of material, e.g. biomolecules may be complete or partial. For example, 10% of the thin layer of material present on the shaping surface may be transferred to the polymer article upon bringing the heated polymer, i.e. soften and/or melted, in contact with the shaping surface where the thin layer of material was applied to form the polymer article.

In some other embodiments a range between 10% and 50% of the thin layer of material applied to the shaping surface may be transferred to the polymer article formed upon bringing the heated polymer in contact with the shaping surface. Prefereably more than 50% of the thin layer of material present on the shaping surface is transferred to the polymer article formed upon bringing the heated polymer in contact with the shaping surface.

Topographical clearness is herein defined as having a surface roughness of less than 300 nm, more preferably less than 200 nm, even more preferably in the range between 100 nm and 0 nm. A topographically clear surface allows for optimal replication of thin films of heat sensitive materials, where replication is defined as the process of transferring the thin film of heat sensitive material to the polymer article during shaping of the polymer article.

A polymer article is herein defined as an article, e.g. a container or part of a container or a part of a medical device, or a functional part of a medical device where functional is intended as being able to change the surface properties of the material, e.g. changing the hydrophilicity or binding properties or sensing properties, or being able to promote biological activities or facilitating biological process, formed by heating, shaping and cooling a polymer, e.g. a thermoplastic material. Non-limiting examples of thermoplastic polymer that may be used are acrylonitrile butadiene styrene (ABS), acrylic, celluloid, cellulose acetate,

Ethylene-Vinyl Acetate (EVA), Ethylene vinyl alcohol (EVAL), Fluoroplastics, Liquid Crystal Polymer (LCP), polyacetal, polyacrylate, polyacrylonitrile, polyamide, polyamide-imide (PAI), polyaryletherketone, polybutadiene, polybutylene, polybutylene therephthalate, polycaprolactone (PCL), polychlorotrifluoroethylene (PCTFE), polyethylene terephthalate (PET), polycyclohexylene dimethylene terephthalate (PCT), polycarbonate (PC), polyhydroxyalkanoates (PHAs), polyketone (PK), polyester, polyethylene (PE), polyetheretherketone (PEEK), polyetherimide (PEI), polyethersulfone (PES), Polyethylenechlorinates (PEC), polyimide (PI), polylactic acid (PLA), Polymethylpentene (PMP), polyphenylene oxide (PPO), polyphenylene sulfide (PPS), polyphthalamide (PPA), polypropylene (PP), polystyrene (PS), polysulfone (PSU), polyurethane (PU), polyvinyl acetate (PVA), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC) and styrene- acrylonitrile (SAN), or mixes or copolymers thereof.

In a preferred embodiment the polymer article is formed from a biodegradable polymer, such as a biodegradable thermoplastic. Biodegradability may be defined by standards well known in the art, such as ASTM D4300, which is a test method designed to be used to determine the susceptibility of polymers to biodegradation.

The heat sensitive material may be selected from the group of materials where a structural change in their macromolecules takes place upon heating of the material in a range between 100° and 250°C for at least 5 seconds. Heat sensitivity is defined in respect to water. Heat sensitivity tested in the presence of water, where the presence of water is defined by the level of water present when passively adsorbing the heat sensitive material to a polymer surface from an aqueous solution with subsequent drying for 1 minute in a flow of gaseous, dry nitrogen under conditions that do not adversely affect the heat sensitive material or the polymer substrate. For the material to be considered a heat sensitive material the structural change in the macromolecule preferably leads to

denaturation or degradation of the material, i.e. the functionality of the material is impaired upon heating. Heat sensitive materials experiences therefore

degradation or denaturation upon heating over a temperature which depends on the type of materials.

An heat sensitive material is considered not adversely affected when the shaping surface is maintained at a temperature such that it is not more than 50% degraded or denaturized by contact with the heated polymer, preferably not more than 30% degraded or denaturized even more preferably not more than 20% degraded or denaturized, even more preferably in the range between 10 and 0%. The heat sensitive material may be also considered not adversely affected when the shaping surface is maintained at a temperature such that the heat sensitive material does not more than 50% loose its binding properties to the polymer article surface, preferably not more than 30%, even more preferably not more than 20%, even more preferably in the range between 10 and 0%.

The heat sensitive material may be also considered not adversely affected when the shaping surface is maintained at a temperature such that the heat sensitive material does not loose more than 50% of its chemical or biological activity, preferably not more than 20%, even more preferably in the range between 10 and 0%.

In some embodiments the heat sensitive material is a biomaterial, e.g. one or more biomolecule, i.e. any organic molecule that is produced by a living organism. In some embodiments the heat sensitive material is selected from the group consisting of peptides, hormones, proteins, nucleic acids, lipids and carbohydrates or structures containing these, e.g. living cells. In other embodiments the heat sensitive material is or is part of components that increase adhesion of cells to surface (including the polypeptide polylysine), antibodies (mono- or polyclonal) and complement factors.

In some other embodiments the heat sensitive material changes physical and chemical properties, e.g. hydrophobicity or lipophilicity, of the polymer material used for producing the polymer article. Examples of these sensitive materials are bovine serum albumin (BSA) or Polyethylene glycol (PEG).

The shaping surface depends on the method of production of the polymer article. An example of shaping surface may be a shim when an injection molding process is used for the production of the polymer article. Another example of shaping surface may be a roller when the process used for the production of the polymer article is a calendering process.

The shaping surface may have a plane or textured primary form. Textured refers to the desired structure or pattern, i.e. a random or systematic pattern of elevated and depressed areas, of the shaping surface. Roughness majorly influences the interaction between the shaping surface and the polymer article.

Surface roughness is herein defined as the vertical deviations of a real surface from its primary form. Large deviations defines a rough surface, low deviations define a smooth surface. Roughness can be measured through surface metrology measurements. Surface metrology measurements provide information on surface geometry. These measurements allow for understanding of how the surface is influenced by its production history, (e.g., manufacture, wear, fracture) and how it influences its behavior (e.g., adhesion, gloss, friction).

Surface primary form is herein referred as the over-all desired shape of a surface, in contrast with the undesired local or higher-spatial frequency variations in the surface dimensions. Example on how to measure surface roughness are included in the document from the International Organization for Standardization ISO 25178 which collects all international standards relating to the analysis of 3D areal surface texture.

Roughness measurements can be achieved by contact techniques, e.g. by use of profilometers or atomic force microscope (AFM), or by non-contact techniques, e.g. optical instruments such as interferometers or confocal microscope. Optical techniques have the advantages of being faster and not invasive, i.e. they do physically touch the surface which can not be damaged.

Surface roughness values herein referred are intended as to be the values of the maximum peak to valley height of the profile along the surface primary form within a 10 μηι sampling length. The values of maximum valley depth are defined as the maximum depth of the profile below the mean line along the surface primary form sampling length and the values of the maximum peak height are defined as the maximum height of the profile above the mean line along the surface primary form sampling length.

In some embodiments the shaping surface is made of steel. Steel is a very hard material and has a high resistance to abrasion so that generally in order to achieve low values of surface roughness it is know to cover steel shaping surfaces with a more ductile material, e.g. Nickel. For example Nickel has been

electroplated on top of glass shaping surface achieving a very low surface roughness which does not need any further treatment.

The shaping surfaces used in the present method are treated with a method that reduces drastically the surface roughness of shaping surface made with hard materials, e.g. steel.

For example treating of the shaping surface may involve wet chemical processes as isotropic etching, e.g. polishing etch. Another example of a method for treating the shaping surface may be mechanical polishing.

One way of polishing the shaping surface made of hard materials comprises: bringing in contact the shaping surface with abrasive particles, e.g. nanoparticles of hard materials, rubbing the shaping surface with these abrasive particles by applying a certain degree of force.

Rubbing is defined as moving abrasive particles over the shaping surface with pressure so as to cause friction and therefore produce a desired degree of abrasion. Rubbing may be exploited manually or mechanically and this determines the degree of force used. Rubbing may be also exploited by rotating means on which abrasive particles are deposited or embedded.

Abrasive particles may be made of hard materials such as flint, garnet, emery, alumina, alumina-zirconia alloy, titania, ceria, silicon carbide or chromium oxide and diamond.

Particle size of these abrasive particles may be in the range between 1 μΐη to 1 nm, preferably less than 1 μηη, more preferably less than 100 nm, even more preferably less than 10 nm.

In some embodiments such abrasive particles may be embedded in plastic films, papers, cloths or vulcanized fibers, having a disc, belt or foil shape. These materials supporting the abrasive particles may be flexible with the advantage of being able to follow irregular contours of the shaping surface.

In some other embodiments said abrasive particles may be included into a colloidal phase such as an abrasive paste.

In one embodiment of the invention the method according to first aspect, further comprises assembling the at least one polymer article with at least one polymer member to form a polymer container.

A polymer member is herein defined as a constituent part of a container, e.g. a wall, a lid, top or bottom. When the polymer article is a complete container in itself the polymer member maybe an additional constituent of the container which provide further functionality to the container, e.g. separator which may divide the container into subunits.

Polymer article and member may be plane or textured. The polymer container may be closed or open, a plane part may be connected to a structured/textured or to a plane or vice versa. The heat sensitive material may be transferred either to a plane or to at least partially textured surface of the polymer article. Herein textured surface of the polymer article is defined as a random or systematic pattern of elevated and depressed areas of the polymer article. Preferably, such texture includes formations having at least one relatively small dimension, such as width. Such a dimension may for instance be less than 1 mm, more preferably less than 100 μηη, more preferably less than 10 μηη, e.g. less than 1 μηη, possibly less than 100 nm. Such features may form lines or spots, reticulated networks, islands, islands connected by lines, or mixtures thereof. Spacing between elevated features may be less than 1 mm, more preferably less than 100 μηη, more preferably less than 10 μηη, e.g. less than 1 μηη, possibly less than 100 nm.

A polymer container may contain at least one fluid such as biological growing medium.

In other embodiments the assembling comprises bringing in contact said at least one polymer article with the at least one polymer member and laser welding the at least one polymer article with said at least one polymer member.

Laser welding is a known welding technique used to join multiple pieces of materials through the use of a laser. The beam provides a concentrated heat source, allowing for narrow, deep welds and high welding rates. The process is particularly advantageous when used in high volume applications for its rates and precision. Another advantage in using a laser welding technique is that such a technique does not affect the properties of the heat sensitive materials. On the contrary other welding techniques like ultrasonic welding may affect the heat sensitive material properties.

In other embodiments the laser welding comprises inserting the at least one polymer article in contact with the at least one polymer member in a packaging comprising a member formed of an air tight and flexible sheet transparent to the laser employed in the laser-welding; exerting a pressure lower than the

atmospheric pressure between the at least one polymer article in contact with the at least one polymer member and said air tight and flexible sheet; maintaining said polymer article and said polymer member in contact applying pressure means laser welding through said packaging the at least one polymer article with the at least one polymer member contained in the packaging.

In some embodiments the polymer article and the polymer member are kept in contact simply by the lower pressure present in the packaging.

In some other embodiments the pressure means applied to maintain the polymer article and polymer member in contact may be devices with the function of applying a certain degree of physical pressure between the polymer article and the polymer member, e.g. clamps. In some embodiments the packaging where at least one polymer article in contact with the at least one polymer member is the final packing in which the polymer container laser welded is contained to be stored and put on the market.

The transmittance properties of the flexible sheet allows for laser welding through the packing without any influencing the mechanical, physical and/or chemical properties of the packaging. This is possible as the laser is absorbed only at the colored interface between the at least one polymer article and at least one polymer member, but it is not absorbed by the packaging which has a certain degree of transparency to the within the range of the light emitted by the Laser. This specific laser welding process described has the advantage of reducing dramatically the speed of production of a polymer container. Through this process the packaging step precedes the laser welding step which therefore becomes the final step of the process before the polymer container can reach the market.

Generally in order to keep polymer articles in contacts with polymer members clamps or other devices with the function of applying a certain degree of physical pressure between the polymer article and the polymer member are employed. By introducing the packaging step before the laser welding and by reducing the pressure in the package, full contact between the polymer article and polymer member is kept by the flexible and air tight sheet which adhere to the polymer article in contact with the polymer member under the external pressure. Therefore the laser welding speed rate is greatly increased as there is no need of

complicated supporting systems to keep in contact the polymer article and member as the packing in itself exploits the function of bringing and keeping them in contact.

In some embodiment the pressure exerted is a vacuum. In some other

embodiments the pressure is lower than the atmospheric pressure so as to allow adherence of the flexible and air tight sheet to the polymer article in contact with the polymer member.

The degree of transparency of the air tight and flexible sheet may be 100%-10% transmittance within the range of the light emission of the laser employed.

The packaging may be formed by a support member, e.g. a flat air tight semirigid member, and a cover member, e.g. an air tight flexible sheet adhered by its periphery on the support member. In other embodiments the packaging may be formed by an air tight flexible bag, i.e. all the packaging is made by air tight flexible materials.

In some other embodiments the welding is performed employing a laser within a wavelength range absorbable by at least part of the polymer container or polymer member.

Polymer member or polymer article may be partially or fully transparent to the laser beam. The absorption of polymer within the Ultra Violet (U.V.), visible and Near Infra Red (N.I.R.) range is determined by the polymer or polymer blends used for producing the polymer article or member. Polymer articles or members may have been produce including other materials, e.g. fillers, which have the property of absorbing light within a specific wavelength range, e.g. the one of the laser beam used. Being able to control the adsorption of the polymer articles and members has the advantage of greatly facilitate the assembling and speed/rate of welding as the container can be assembled without complicated system. Being the laser beam selectively absorbed, there is no need of particularly geometries or complicated system in welding.

In some embodiments the polymer article is produced by injection molding.

Injection molding is performed by heating a suitable polymer until molten, injecting the molten polymer into a mold, allowing the polymer to cool and harden, and removing the molded article from the mold. This process may be automated and therefore used to produce a rapid succession of identical articles. The mold used may have means for cooling, in order to increase the speed of hardening of the polymer. A removable shaping surface, e. g. a shim may be incorporated into the mold, and this shim may bear surface structure and/or texture that are transferred to the polymer article during the molding process. Alternatively, such structure may be present on the mold so that the mold in itself may be the shaping surface.

In some other embodiments the method for producing polymer article is calendering. Calendering is a process used to manufacture polymer sheeting. A suitable polymer in pellet form is heated so as to soften and/or melt it at least partially and forced through a series of heated rollers until the polymer sheet reaches the desired dimensions. The sheeting is then passed through cooling rollers in order to cool and set the polymer. Frequently, texture is applied to the polymer sheet during the process, or a strip of fabric is pressed into the back of the polymer sheet to fuse the two together. The calendering process may be used in combination with extrusion - the extruded polymer form may be passed through the heated rollers of the calender as above until the required dimensions are obtained, and then passed over cooling rollers to set the form of the polymer. All of the features described may be used in combination so far as they are not incompatible therewith. Thus, injection molding, compression molding and calendering may be used combined, e.g. part of the process may be carried by injection molding and part by calendering.

In some other embodiments the heat sensitive material is applied on the shaping surface by absorption from fluids.

Adsorption from fluids involves leaving the shaping surface for a certain period of time in contact with the fluid containing the heat sensitive materials, e.g. by submerging the shaping surface in the fluid or by depositing the fluid onto the shaping surface through a depositing device.

In some embodiments the heat sensitive material is applied on the shaping surface by inject printing. Inject printing is the process by which variably-sized droplets of liquid or molten material, e.g. heat sensitive materials are propelled onto almost any surface, e.g. a shaping surface.

In some other embodiments the heat sensitive material is applied on the shaping surface by contact printing. Contact printing is defined as the process through which a material present on a flexible stamp is transfer onto a shaping surface by bringing them in contact and supplying energy to the combined system. Energy may be supplied in different form, e.g. by heating or by applying a pressure on the stamp.

Other method of application of the heat sensitive material may be dry deposition or by drying a liquid solution previously deposited.

Fluid may be a liquid, with different degrees of viscosity a vapor or a gas.

In some embodiments absorption may be mechanically induced. For example by mechanically confining the liquid solution containing the heat sensitive material to be adsorbed, it is possible to reduce the amount of solution to be used and therefore reduce the costs of production. Mechanical confinement is defined as confining the liquid solution within a desired volume by use of articles, e.g. plates positioned on top of the shaping surface, or other devices.

In another aspect the invention provides a polymer article produced by the method according to any of the preceding claims comprising an integrated detection system for detecting interaction with the biomaterial transferred onto the polymer article surface. The polymer article produced may be part of a larger sensor system, e.g. system which can measure Surface Plasmon resonance (SPR) or system which uses interferometric techniques.

In some embodiments of the invention the detecting system allows for detection of biomolecules or cells specifically bound to the biomaterial transferred onto the polymer article surface.

In some embodiments the invention provides a polymer article produced by the method according to any of the preceding claims, wherein said material is not covalently bond, nor antibody/antigen bond, neither ligand bond to the polymer article and is not at least partially removable from the surface of the polymer article upon application of a fluid flow at a speed of 120 mm/sec applied for 5 sec in a 140 pm height channel which is 1 cm wide.

"Being not at least partially removable" from the surface of the polymer article is herein defined as a material that following the application of the specific fluid flow previously mentioned is not removable more than 50%, preferably not more 25%, even more preferably not more than 15%, even more preferably not more than 5% of its previous surface coverage of the polymer. Alternatively "being not at least partially removable" may be also defined as that the material retains his activity more than 50%, preferably more than 75%, even more preferably more than 85 %, even more preferably more than 95% of its activity before the fluid flow.

In another aspect the invention provides an injection molding system for producing a polymer article characterized in that the shaping surface used has a surface roughness of less than 300 nm, more preferably less than 200 nm, even more preferably in the range between 100 nm and 20 nm, e.g. between 50 and 20 nm. In some embodiments the shaping surface used has a surface roughness of less than 20 nm. In another aspect the invention provides a method for laser welding at least two polymer members comprising : inserting a first polymer member in contact at least with a second polymer member in a packaging comprising a member formed of an air tight and flexible sheet transparent to the laser employed in the laser- welding ;exerting a pressure lower than the atmospheric pressure between said at least two polymer members in contact with each other and the air tight and flexible sheet; maintaining said first polymer member and said second polymer member in contact applying pressure means; laser welding through said packaging said at least two polymer members in contact with each other contained in said packaging.

The first, second and other aspects of the present invention may each be combined with any of the other aspects. These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.

BRIEF DESCRIPTION OF THE FIGURES

The method according to the invention will now be described in more detail with regard to the accompanying figures. The figures show one way of implementing the present invention and is not to be construed as being limiting to other possible embodiments falling within the scope of the attached claim set.

Figure 1 shows a cross section of the shaping surface according to different steps of the method for producing a polymer article of herein described.

Figure 2 shows a cross section of the shaping surface according to the injection molding process herein described.

Figure 3 shows a cross section of the injection mold system according to one embodiment of the invention.

Figure 4 shows a cross section of the calendering system according to one embodiment of the invention.

Figure 5 shows a method to keep in contact a polymer article and a polymer member or more members for laser welding purposes according to one

embodiment of the invention.

Figure 6 is a flow-chart of a method according to one aspect of the invention. DETAILED DESCRIPTION OF AN EMBODIMENT

Figure la shows a shaping surface 1, e.g. a shim presenting a surface 8 with high level of surface roughness. Following the polishing process as previously described, the shim is shown in figure lb having a surface 8 which achieved a topographical clearness. The heat sensitive material (e.g. Collagen) is dissolved in an appropriate solvent, e.g. de-ionised water, in a concentration of e.g. 10 pg/ml providing a homogeneous solution. The solution is deposited onto the shim 1 in an array of drops 2 and 3 as shown in figure lc. While two drops are shown as an example, any number of drops may be used. After being in contact with the shim 1 for a certain period of time, e.g. 5 minutes, the drops 2 and 3 are evaporated from the shim 1 by blowing dry compressed air parallel to the shim surface 8 as shown by arrow 9 in figure lc. The shim 1 now contains a corresponding array of surface adsorbed collagen 6 and 7 as shown in figure Id. The shim 1 may be textured or plane, and may form a removable or a permanent part of a mold. The shim and/or the mold may additionally have macroscopic surface structure, in addition to the surface texture. For example, the shim and/or mold may be shaped to form a multi-well plate from the polymer, in which the bottoms of the wells are smooth or textured. The shaping forming the wells is the macroscopic structure, and the texture of the shim forms the texture of the bottom of the wells, and may be termed the microscopic structure.

Once the desired combination of materials has been applied to the shim, the shim 1 is inserted into the mold 5 as shown in figure 3. A molten polymer 4 is then introduced into the mold 5 according to the injection molding technique as shown in figure 2a and figure 3. The molten polymer 4 fills the cavity 11 and gets in contact with the shim 1. The time from the removal of the excess solvent to the introduction of the molten polymer is preferably as short as possible, and in this embodiment less than 30 s.

The molten polymer 4 is allowed to remain in the mold until it has cooled and set (figure 2b). This time may be of the order of a minute or less. After setting, the materials 6 and 7 have been transferred from the shim 1 to the surface of the polymer according to the pattern and topography with which the materials were placed on the shim 1. The polymer article 10 is removed from the mold as shown in figure 2c, and the materials deposited on its surface 6 and 7 may be detected by appropriate methods. Examples of polymer articles may be container for biological growth or implants, part of implants, or can be used to cover and protect implants or part of implants, e.g. plates for implants application, biocompatible screws, and backbone disks.

For example an injection molding was performed on an Engel 25 tons machine fitted with a water-cooled mold with a replaceable shim. The dimensions of the shim were radius 85 mm, with a 300 pm thickness. The shim was supported by a highly heat-conducting backplate. The shim was polished following the method of according to the invention and surface roughness of between 5-10 nm was measured. After application of the biomaterial, streptavidine, to be transferred, the shim was mounted in the mold and the polymer injected into the mold. The water cooling was set to the minimum temperature, yielding a mold temperature of 26 °C before injection of the molten polymer. The mold temperature was monitored via a thermistor in the backplate and increased to approximately 30 °C during injection of the molten polymer. The polymer article was removed from the mold after a cooling time of 60 s. The melt temperature used for polystyrene was 250 °C. It was analysed that 95% of the biomaterial was transferred from the shim to the polymer.

Figure 4 shows an apparatus for incorporation into a calender, preferably between the heated rollers and the cooling rollers. The desired material may be transferred to the surface of a shaping roller 12 by submersing a part of this in a bath 13 containing the solution of the heat sensitive material 14. The polymer 4 forced between shaping roller 12 and shaping roller 15 receives the heat sensitive material 14 by contact with shaping roller 12. In this way the heat sensitive material 14 is transferred to the surface of the polymer 4. The surfaces of the shaping roller may be textured, and so different topographies on the surface of the polymer 4 may be obtained. As many biologically-active molecules' biological activity is destroyed by exposure to high temperatures - for example, some proteins are denatured at temperatures above 40°C - the shaping rollers are preferably maintained at a temperature of about 30°C or lower during contact with the heated polymer 4. Alternatively, compounds that modify the surface characteristics of the polymer may be used, such as polymer coatings that reduce or enhance the residence time of a substance on the polymer surface without reacting with that substance. Figure 5a shows a polymer article 16 on which a polymer member 17, e.g. a series of open cylinder, shown in figure 5b, is laser welded. The method of laser welding as herein described includes the insertion the polymer article 16 in contact polymer member 17 in a packaging 18, which in this embodiment is shown as an air tight and flexible container. By reducing the internal pressure through the opening 19, e.g. by applying vacuum condition through the

application of a vacuum pump to the opening, polymer article 16 and polymer member 17 are kept in tight contact by the adhesion of the packaging 18 under an external pressure, e.g. 1 atm, which is higher than the pressure inside the packaging. In this way the polymer article and member can be laser weld while contained and kept in contact through the packaging 18.

Figure 6 is a flow chart of the method according to one aspect of the invention. The method to produce a polymer article comprising at least one heat sensitive material provided onto at least part its surface comprises treating, e.g. polishing, a shaping surface to achieve topographical clearness (SI), applying at least one heat sensitive material onto at least one part of the shaping surface (S2), bringing the heated polymer in contact with the shaping surface to form the polymer article (S3) and removing the polymer article after the shaping (S4).

Although the present invention has been described in connection with the specified embodiments, it should not be construed as being in any way limited to the presented examples. The scope of the present invention is set out by the accompanying claim set. In the context of the claims, the terms "comprising" or "comprises" do not exclude other possible elements or steps. Also, the mentioning of references such as "a" or "an" etc. should not be construed as excluding a plurality. The use of reference signs in the claims with respect to elements indicated in the figures shall also not be construed as limiting the scope of the invention. Furthermore, individual features mentioned in different claims, may possibly be advantageously combined, and the mentioning of these features in different claims does not exclude that a combination of features is not possible and advantageous.

All patents and non-patent references cited in the present application are also hereby incorporated by reference in their entirety.