DE102005054704A1 - Producing amorphous carbon layer of controlled thrombogenicity, by deposition in magnetron sputtering plant to give thrombocyte enriching or repelling layer depending on surface energy - Google Patents

Abstract

In the production of an amorphous carbon layer (I), on a substrate (II) by positioning (II) in the processing chamber of a magnetron sputtering plant, plasma-etching and depositing (I) from a graphite target onto (II), the thrombogenicity of (I) is adjusted so that the surface energy is below or above a threshold value of 34.4 mN/m to give a thromobocyte enriching or thrombocyte repelling layer (I) respectively. Production of an amorphous carbon layer (I), containing at most 5 atomic % hydrogen, on a substrate (II) involves: (a) grinding, polishing and cleaning (II); (b) positioning (II) in the processing chamber of a magnetron sputtering plant and evacuating the chamber; (c) plasma-etching (II); and (d) depositing (I) from a graphite target onto (II) under an argon partial pressure of 0.2-2.0 Pa. The novel feature is that the thromogenicity of (I) is adjusted such that the surface energy is below or above a threshold value of 34.4 mN/m to give a thromobocyte enriching or thrombocyte repelling layer (I) respectively.

Description

The The invention relates to a platelet-repellent layer on a Substrate, a process for its preparation and a medical Instrument or implant to which applied such a layer is.

immediate after the contact of a medical instrument or Implant with blood becomes on its surface a layer of proteins adsorbed from the blood plasma, the following in particular with the activation of the coagulation and Complement system of the blood, with inflammatory reactions and associated with cell attachment.

Out the addition of adsorption proteins HMWK (High Molecular Weight Kiniogen) or albumin results in reduced adhesion and Activation of blood cells (platelets, monocytes, granulocytes). The Tissue response to a substrate that is crucial to the question and duration of its use (long-term stability and biocompatibility), does not hang only from its surface, but also from the resulting layer of adsorbed proteins from. For the composition of this protein layer are the substrate and the nature of its surface responsible.

The Measure of Platelet rejection or accumulation (thrombogenicity) on one surface a medical instrument or an implant provides one the most important criteria for assessing biocompatibility Release of thrombogenic substances may cause a massive coagulation disorder (hypercoagulability), d. H. an increased coagulability of the blood up to thrombotic closures cause. In Germany alone, around 30,000 people die each year at the consequences of a pulmonary embolism.

Out P. Yang, N. Huang, Y.X. Leng, J.Y. Chen, R.K.Y. Fu, S.C.H. Kwok, Y. Leng and P.K. Chu, Activation of platelets adhered to amorphous hydrogenated carbon (a-C: H) films synthesized by plasma immersion ion implantation deposition (PIII-D), Biomaterials 24 (2003), p. 2821-2829, is a process for producing amorphous carbon films using PIII-D (plasma immersion ion implantation and deposition) known.

S.C.H. Kwok, J. Wang and P.K. Chu pose in Surface energy, wettability, and blood compatibility of phosphorus doped diamond-like carbon film, Diamond, Relat, Mater. 14 (2005), pp. 78-85, a method for producing phosphorous-doped amorphous carbon layers by means of PIII-D.

T. Saito, T. Hasebe, S. Yohena, Y. Matsuoka, A. Kamijo, K. Takahashi, and T. Suzuki, Antithrombogenicity of Fluorinated Diamond-Like Carbon Films, Diamond. Relat. Mater. 14 (2005), p. 1116-1119, a method for the production of fluorine-doped amorphous carbon layers by means of chemical vapor deposition (CVD) with C ₂ H ₂ and C ₂ F _{6 is} known.

T.I.T. Okpalugo, A.A. Ogwu, P.D. Maguire and J.A.D. McLaughlin show in Platelet adhesion on silicon modified hydrogenated amorphous carbon films, Biomaterials 25 (2004), pp. 239-245, a process for the preparation of silicon-doped amorphous carbon layers by means of plasma enhanced chemical vapor deposition (Plasma Enhanced Chemical Vapor Deposition, PECVD).

M. I. Jones, I.R. McColl, D.M. Grant, K.G. Parker and T.L. Parker reveal in protein adsorption and platelet attachment and activation on TiN, TiC and DLC coatings on titanium for cardiovascular applicatons, J. Biomed. Mater. Res. 52 (2000), pp. 413-21, a method of preparation of amorphous carbon layers by ion plating with acetylene.

task The invention is a platelet-repellent layer on a Substrate, a process for its preparation and a medical Instrument or implant to which applied such a layer is to indicate.

These Task is solved with regard to the layer by the features of claim 1, with regard to the method by the steps of claim 8 and with regard to the medical instrument or implant the claim 12. The dependent claims give each advantageous embodiments of the invention.

The layer according to the invention is applied to a substrate. All materials which can be in direct or extracorporeal contact with tissue are suitable for this purpose. These include metals or alloys, preferably Ti, Ti6A14V, NiTi, TiAl, gold, alloyed or unalloyed (noble) steels. Also suitable are glassy or ceramic substrates such as glassy carbon (Sigradur-G, Sigradur-K), SiC, Si ₃ N ₄ , AlO ₂ or ZrO ₂ . Due to the low process temperature of 50 ° C to 200 ° C are also substrates of plastics (polymers), in particular Teflon (PTFE), polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), Acryinitrilmethylmethacrylat (AMMA), polyamide (PA), polyimide (PI ), Polycarbonate (PC), polyvinyl chloride (PVC), polypropylene (PP), polyurethane (PU) or polyethylene (PE). The substrate itself may be fixed or detachably connected to another pad.

The inventive layer consists of an amorphous carbon layer whose surface energy above a threshold of 34.4 mN / m, the surface energy a value up to and including 47.7 mN / m.

Of the polar fraction of the surface energy is here from 5 mN / m to 8.9 mN / m. All values for the surface energy, that are specified in this document were after the procedure from D.K. Owens, R.C. Wendt, J. Appl. Polym. Sci. (1969), p. 1741-1747, certainly.

The present invention makes use of that found by the inventors and in the 1 shown relationship between the surface energy and the degree of adherence of platelets on layers according to the invention. The surface energy obviously has a critical value for the degree of adherence of platelets on the surface at about 34.4 mN / m. Only the discovery of this fact makes it possible to set a surface of a substrate which has been coated according to the invention in a simple and economical manner with regard to its behavior towards thrombogenicity.

Related to the discovery of this issue is the position of the G band of a Raman spectrum in the visible range (excitation wavelength of 514.5 nm), which in 2 is plotted as a function of the number of adherent platelets. For a layer according to the invention, the G band is in the range of 1550 cm ^-1 to 1560 cm ^-1 .

The inventive layer has a layer thickness of 50 nm to 10 .mu.m, preferably from 100 nm to 5 μm, especially preferably from 500 nm to 2 μm on.

In a preferred embodiment has the inventive layer a content of hydrogen of at most 5 atomic%, by means of Nuclear Reaction Analysis (NRA) can. Thus, this layer is virtually as hydrogen-free.

The hardness of the layer according to the invention is from 5 GPa to 40 GPa. The Electron Energy Loss Spectroscopy (EELS) specific sp ³ bond fraction of the layer of the present invention assumes a value in the range of 0% to 30%.

The roughness of the film of the present invention when viewed from the average roughness R _a from 3 nm to 23 nm, the smoothing depth R _p of 16 nm to 200 nm, the root mean square R _q of 6 nm to 27 nm, the difference R _t between the highest peak to the deepest groove from 29 nm to 170 nm and the average roughness R _{z (ISO)} from 20 nm to 190 nm.

The (advancing) wetting angle of the layer according to the invention for H ₂ O _dest assumes a value of 65 ° to 77 ° and for formamide from 50 ° to 59 °.

In a particular embodiment, the layer according to the invention has an adherence of platelets of at most 2000 platelets (platelets) per mm ² , preferably of at most 1000 platelets (platelets) per mm ² .

The The present invention further relates to medical instruments or implants that serve as a substrate and in each case at least partially are coated with at least one or more layers according to the invention. This includes Short or long-term implants, in particular stents, bone anchors, vein filters, vascular clips, Aneurysm stents, coronary or venous valves and valve systems, Zahnregulierdrähte or mechanical bypass connections. Also suitable are medical Instruments for open or minimally invasive surgery, e.g. scissors, Forceps, retractors, scalpels, needles, biopsy instruments, catheters or needle holder as a substrate.

• a) Vorbehandeln des Substrats,
• b) Positionieren des Substrats in einer Prozesskammer,
• c) Plasmaätzen des Substrats und
• d) Beschichten des Substrats.

The method according to the invention for producing a platelet-repellent layer on a substrate is carried out according to the following steps a) to d):

• a) pretreatment of the substrate,
• b) positioning the substrate in a process chamber,
• c) plasma etching of the substrate and
• d) coating the substrate.

The provided substrate is first according to step a) a pretreatment subjected. The substrate is here ground and polished to one possible homogeneous surface to produce and purified. In particular, should in the light microscope neither material accumulation, which by different hard components z. In alloys be formed, nor a formation of pores, surface damage or Scored by liberated Components are recognizable.

After the pretreatment, the substrate is introduced according to step b) into a process chamber of a magnetron sputtering system and aligned (positioned) in the process chamber for the subsequent process steps. Subsequently, an evacuation of the process chamber. The evacuation is preferably carried out until the process chamber (recipient) has only a residual gas pressure of 1 × 10 ^-4 Pa to 4 × 10 ^-4 Pa.

In In the process chamber, the substrate is first subjected to a plasma etching process in accordance with step c) subjected. The working gas used is preferably argon at an argon partial pressure from 0.2 Pa to 2.0 Pa.

Finally, according to step d), the deposition of the amorphous carbon layer from a graphite support onto the pretreated, positioned and plasma-etched substrate takes place. For this purpose, an argon partial pressure of 0.2 Pa to 2.0 Pa and a sputtering power per unit area of 7.92 to 15.58 W / cm ^{2 are} set.

The Coating process is preferably carried out at a temperature of 50 ° C to 200 ° C, particularly preferred from 70 ° C up to 150 ° C, carried out. The thus provided with an amorphous carbon layer Substrate can after pressure equalization and cooling on at the most 60 ° C, preferably to room temperature, the coating system are removed.

The inventive method allows different geometries, both in two dimensions (planar) as well as in three dimensions (spatially) to coat.

The Invention will be described below with reference to exemplary embodiments with the aid the pictures explained in more detail. It demonstrate:

1 Platelets per mm ² as a function of the surface energy of platelet repellant and platelet enrichment layers.

2 Platelets per mm ² as a function of the position of the G-Raman band of platelet repellant and platelet enrichment layers.

1 shows a representation of the relationship between the surface energy and the platelet adherence of platelet-repellent layers of the invention and - as a comparison - of platelet-enriching layers. With a surface energy below the detected threshold value of 34.4 mN / m, a strong platelet adherence (platelet enrichment), with a surface energy above the detected threshold of 34.4 mN / m, however, a weak platelet adherence (platelet rejection) is observed.

In 2 the dependence of the number of adherent platelets on the position of the G-Raman band is shown. Raman spectroscopy is very sensitive to small amounts of sp ² bonding in diamond or amorphous carbon layers. Pure diamond, which has exclusively sp ³ -configured carbon bonds, has a discrete line at 1332 cm ^-1 , whereas pure graphite, which has exclusively sp ² -configured carbon bonds, has a 1580 cm ^-1 , which in the case of of graphite is referred to as G-band (graphite peak). The shift in the position of the G-band to lower wavenumbers is correlated with the reduced accumulation of platelets.

The Raman spectra were recorded with a commercial Raman spectrometer at 514.5 nm excitation wavelength (argon ion laser). Prior to measurement, calibration was performed on a silicon wafer with a well-defined surface, which contributed a single discrete band 520 cm ^-1 . The samples were cleaned with isopropanol prior to measurement. The recorded spectra were recorded under Ver Adjusted to a linear baseline with two Gaussian peaks, the parameters band height, width, and position were not fixed during iterative fitting. The curve fitting converged after about 10 iterations.

Pretreatment of the substrates

The used substrates made of silicon, the carbide WC-Co, the stainless steels Ti6A14V and a chromium-containing stainless steel with admixtures of Mn (material number: 1.4034, X46Cr13) were depending on the type and quality of the surface of the Materials of a complex Subjected to the procedure of grinding and polishing.

The roughness (Ra) of the substrates after grinding and polishing was:

The Substrates were each placed in an ultrasonic bath for 15 minutes prior to coating in acetone and then purified in isopropanol. Thereafter, the substrates were with distilled Rinsed off water. The Substrates were only handled with latex gloves to transfer from dirt particles and grease through the skin.

Positioning the substrates in the process chamber

Subsequently, the positioning of the substrates in the process chamber of a coating system (magnetron sputtering system) was carried out. The evacuation of the recipient was carried out to a residual gas pressure of 2 × 10 ^-4 Pa.

• 1.) HF (Hochfrequenz) Plasmaätzprozess bei 500 W. Als Arbeitsgas diente Argon, der Druck im Rezipienten betrug 0,6 Pa. Die Parameter wurden über eine Zeit von 20 Min. konstant gehalten.
• 2.) DC-Glowing-Glimmentladung im DC-Feld (direct current) bei einer Gleichspannung (DC-Spannung) von 500 bis 800 V. Als Arbeitsgas wurde ebenfalls Argon eingesetzt, der Druck im Rezipienten betrug auch hier 0,6 Pa. Die genannten Parameter wurden über eine Zeit von 15 bis 90 Minuten konstant gehalten.

Plasma etching of the substrates Before the actual coating, the substrates were cleaned in a plasma etching process. Two methods were used:

• 1.) HF (high frequency) plasma etching process at 500 W. Argon was used as working gas, the pressure in the recipient was 0.6 Pa. The parameters were kept constant over a period of 20 min.
• 2.) DC glowing glow discharge in the DC field (direct current) at a DC voltage of 500 to 800 V. Argon was also used as the working gas, the pressure in the recipient was also 0.6 Pa. The parameters mentioned were kept constant over a period of 15 to 90 minutes.

During the described method were from the substrate surface about 100 nm of the adsorbates or the substrate removed and both at X46Cr13 as well as Ti6A14V achieved a Ra value of 6 nm.

Coating the substrates

The amorphous carbon layers were deposited by magnetron sputtering of one or more graphite targets in pure argon atmosphere at 0.2 to 2.0 Pa on the thus pretreated and plasma-etched substrates at temperatures up to 150 ° C. Both round cathodes with a diameter of 75 and 150 mm, as well as rectangular cathodes with dimensions of 135 × 465 mm or 134 × 496 mm were used. The distance between target and substrate was between 50 and 150 mm, depending on the coating system. For cathodes with a diameter of 75 mm sputtering powers of 50 to 500 W, for a diameter of 150 mm from 100 to 1000 W and for the rectangular cathodes from 1500 to 6000 W were driven. Accordingly, the power density (sputtering power per unit area) was generally between 0.57 and 13.58 W / cm ² , whereby a power density of at least 7.92 W / cm ^{2 was} required to obtain a platelet-repellent layer of the present invention.

The Layers were deposited with RF substrate bias voltages from 0V to -200V, these are in the range to -200 V does not significantly affect the power density. The value of Pressure only has the effect at low power densities, the surface energy over the Threshold of 34.4 mN / m.

Claims (12)

Platelet-repellent layer on top of a Substrate is applied and an amorphous carbon layer, the a surface energy above a threshold of 34.4 mN / m. The layer of claim 1, wherein the carbon layer has a content of hydrogen of at most 5 atom%. A layer according to claim 1 or 2, wherein the carbon layer has a layer thickness of 50 nm to 10 microns. A layer according to any one of claims 1 to 3, wherein the substrate a surface from a metal, an alloy, a glass, a ceramic or made of a polymer. A layer according to any one of claims 1 to 4, having an arithmetic mean roughness R _a of 3 nm to 23 nm, a smoothing depth R _p of 16 nm to 200 nm, a root mean square R _q of 6 nm to 27 nm, a difference R _t between the highest peak to the deepest of 29 nm to 170 nm and an average roughness R _{z (ISO)} of 20 nm to 190 nm. Layer according to one of Claims 1 to 5, on which at most 2,000 platelets per mm ² accumulate. Layer according to claim 6, to which at most 1000 platelets per mm ² accumulate. A method for producing a platelet-repellent layer on a substrate, comprising the steps of: a) grinding, polishing and cleaning the substrate, b) positioning the substrate in a process chamber of a magnetron sputtering system and evacuating the process chamber, c) plasma etching the substrate, d) depositing an amorphous Graphite carbon layer bears on the thus-treated substrate at an argon partial pressure of 0.2 Pa to 2.0 Pa and a sputtering power per unit area of 7.92 to 15.58 W / cm ² . The method of claim 8, wherein the process chamber is evacuated to a residual gas pressure of 1 · 10 ^-4 Pa to 4 · 10 ^-4 Pa. A method according to claim 8 or 9, wherein the plasma etching of Substrate under argon as working gas at an argon partial pressure of 0.2 Pa to 2.0 Pa. Method according to one of claims 8 to 10, wherein the carbon layer at a temperature of 50 ° C up to 200 ° C is deposited. Medical instrument or implant whose surface at least partially with a platelet repellent layer one of the claims 1 to 7 is provided.