Fraunhofer-Institute for Biomedical Engineering, Sankt Ingbert, Germany

Transcription

1 Investigations on Explanted Micromachined Nerve Electrodes Martin Schuettler*, Klaus Peter Koch, Thomas Stieglitz Fraunhofer-Institute for Biomedical Engineering, Sankt Ingbert, Germany Introduction Micromachining technologies have been used to manufacture neural microelectrodes for roughly a decade. One promising approach utilizes polyimide as a flexible and light-weighted substrate that carries electrode contacts, tracks, and connector pads. Beyond encouraging results, mainly gained in acute animal trials and in vitro tests, the reliability of this technology needs to be proved. The presented study investigates polyimide microelectrodes after several months of implantation focusing on the reliability of used materials and applied technologies. Methods Two different types of micromachined polyimide-based electrodes were implanted in animals and investigated afterwards: regeneration-type electrodes (sieves) that consist of polyimide microsystems glued to silicone nerve guidance channels and Hybrid Cuff Electrodes that are a combination of polyimide microsystems and self-sizing silicone cuff. The following sub-chapters 1.) and 2.) describe the two different types of microelectrodes. Because manufacturing of polyimide microelectrodes was already explained in detail elsewhere ([1], [2]), we describe only the special features of the each type of electrode. Sub-chapter 3) lists the methods applied for investigation of the explanted devices. 1.) Sieve Electrodes The basic structure is a 5 um thin polyimide substrate (Pyralin 2611, HD Microsystems, Bad Homburg, Germany) onto which 10 nm titanium (adhesion promoter) and 300 nm platinum (electrode contacts, tracks, connector pads) were sputtered. A second 5 um layer polyimide was deposited on top and opened at electrode contacts and connector pads. Applying that technology, sieve electrodes were fabricated and implanted without any (non-micromachined) cables or connectors into the sciatic nerve of rats [1]. 2.5 month later, the devices were explanted and examined. 2.) Hybrid Cuff Electrodes A Hybrid Cuff Electrode (HCE) consists of a scaffold-like polyimide substrate, a spiral silicone cuff and a cable. The concept of this electrode is described in detail in [2]. The polyimide substrate (10 um Pyralin 2611) has an integrated metallization layer made of 10 nm titanium, 300 nm gold, and at the electrode contacts additionally 10 nm titanium and 200 nm platinum. All layers were deposited by sputtering. The silicone cuff is composed of a stretched silicone sheet (thickness: 127 um, SSF-METN-050, Speciality Silicone Fabricators, Paso Robles, California) onto which another (slack) sheet was bonded by plasma-bonding technology [3]. The polyimide scaffold was also plasma-bonded to the silicone cuff. The connector pads (each 300 um x 300 um) of the polyimide-scaffold were connected to an adapter by a ballbonding technique, which resembles riveting [4]. The adapter was also made of a polyimide substrate with embedded Ti/Au metallization and enabled through large pads (0.5 mm x 2 mm) direct soldering of stainless steel wires (type AS631, Cooner Wire, Inc., Chatsworth, California) to the sputtered gold layer by using stainless steel solder (type DS , NCH GmbH, Moerfelden-Walldorf, Germany). The surface of the adapter as well as the fluorocarbon (FEP) insulation of the wires were activated by an oxygen plasma to increase surface energy in order to improve adhesion to the subsequently applied silicone encapsulation (MED-1000 adhesive, NuSil, Carpinteria, California).

2 The HCEs finally consisted of silicone cuffs, having polyimide scaffolds bonded to their inner side. One extension of the scaffolds led out of the cuff to the outer side of the cuff wall. Here, the adapter was ball-bonded to the scaffold. Wires were soldered to the adapter. The transition scaffold/adapter/wires was embedded in silicone adhesive which glued that part of the cuff electrode to the outer side of the cuff wall in order to make the whole device one compact unit (Figure 1). Figure 1. Cross-section of Hybrid Cuff Electrode. The HCEs were implanted on peripheral nerves (radial and ulnar nerve) slightly distal to the brachial plexus in goat and explanted after 11 months. 3.) Investigation of Explants Information about material changes and reliability of applied technologies was collected by visual inspection, light microscopy, scanning electron microscopy, tensile strength test, and electrical measurements of impedance. Three sieves and two HCEs were under test. Results a) Material Properties of Polyimide (Sieves and HCEs) Light microscopy and scanning microscopy showed no evidence for cracks in the explanted polyimide, neither after 2.5 months, nor after 11 months. No delamination of the two polyimide layers was observed. Tensile strength of polyimide substrates was determined and related to a control group (same batch of electrodes, but stored in a shelf). Setting the tensile strength of the control group polyimide substrates to 100%, the mean value of the explanted substrates after 2.5 months was reduced to 76.7% and after 11 months to 70.5% (Figure 2). Figure 2. Tensile strength of polyimide substrate as function of implantation time.

3 b) Adhesion of Thin-film Metallization (Sieves and HCEs) The Ti/Pt metallization of the sieves was still adhering well to the polyimide substrate after 2.5 months of implantation. However, the Ti/Au/Ti/Pt metallization of the electrode contacts of the HCEs delaminated in 24 of 36 cases after 11 months of implantation. No delamination of the Ti/Au metallization was observed when the metallization was protected by silicone. c) Material Properties of Silicone (HCEs) No obvious change of the silicone (adhesive and sheets) was found by visual inspection, light microscopy, and during manipulating. No delamination of the plasma-bonded silicone sheets occurred after 11 months. d) Adhesion of Polyimide to Silicone (HCEs) The polyimide scaffolds were completely delaminated from the inner side of the silicone cuffs (sheets) after 11 months. The silicone adhesive still adhered well to the plasma-activated polyimide surfaces. e) Adhesion of Silicone to FEP wire insulation (HCEs) The silicone adhesive still adhered well to the insulation of the wires, but in 4 of 18 cases, the wires were pulled out of the silicone bulk. Three of these wires broke close to the solder joint, one wire was pulled out of the silicone together with the solder bulk. These four wires had in common, that their silicone embedded part was about half the length (1.5 mm) of the silicone embedded part (3 mm) of the other cables. f) Reliability of Ball-Bonding Technique (HCEs) Examination of the transition of the polyimide scaffold to the adapter was carried out only by light microscopy and mechanical tests. No electrical tests could be performed because of lack of access to tracks. In all examined cases (30 bonded contacts in total), no failure of the bonded contacts was found. g) Reliability of Solder Contacts (HCEs) Impedance measurements showed that most wires were electrically disconnected from the polyimide microelectrodes. Light microscopy and mechanical test exposed that the solder (completely covering the pad areas) had no electrical contact to the tracks. The solder possibly absorbed the thin-film of the pads or the thinfilm delaminated from the polyimide substrate but adhered to the solder. The wires were still perfectly embedded in and electrically connected to the solder bulk. h) Reliability of Stainless Steel Electrode Wires (HCEs) 18 stainless steel wires (60 cm each) with FEP insulator were implanted in total. During the explantation, some of the wires were cut and/or the insulator was destroyed. Impedance measurements showed that no cable breakage occurred beside these surgically induced defects. However, three of 18 cables broke close to the solder joint (the braided wires soaked the solder which made them stiff and brittle). Discussion The very small number of systematically characterized microelectrode explants in this study can be considered as insufficient for extracting reliable evaluations of materials and applied technologies. However, we think the presented results at least show which technology can be applied in future implant manufacturing, which have to be improved or even discarded in prospect to upcoming in vivo experiments. We take the study of the polyimide tensile strength as evidence that our type of polyimide undergoes some kind of degradation over time in vivo. The main decay occurs in the first month after which the speed of degradation slows down. Future investigations have to show if the decrease of tensile strength stops at a defined (and acceptable) limit, e.g. at 60% of the initial value.

4 The technology of sandwiching a metallization layer between two layers of polyimide seems to be suitable, because no delamination of the polyimide layers was observed even after 11 months. The right choice of metals for building the electrical conductive elements of the microelectrodes is crucial. Ti/Au/Ti/Pt layers tend to flake off from polyimide while delamination of Ti/Pt layers was not observed. However, adhesion of Ti/Pt layers was investigated after 2.5 months of implantation while Ti/Au/Ti/Pt layers were exposed after 11 months to the biological system. In previous research projects, surgeons also reported on delamination of Ti/Au layers from polyimide substrate after three months. Unfortunately, we had no possibility of inspecting these microelectrodes in our laboratory. In previous in vitro and acute in vivo studies, we gained good results soldering steel wires directly to thin-film metallization. The presented work leaves no doubt that direct soldering to thin-film is not appropriate for longterm implantation purposes. One reason for that may be the diffusion of the thin-film pad metal into the solder bulk. Another possible cause might be the stiffness of the solder compared to the very flexible polyimide substrate and silicone encapsulation: bending movements might cause the solder to break of the polyimide. The thin-film metallization which adheres much better to the solder than to the polyimide also breaks off the polyimide, which cuts the electrical connection to the thin-film tracks. Future designs will use a thick-film ceramic adapter onto which the polyimide scaffold is ball-bonded and the wires are parallel-gap welded, as described in [1]. AS631 wires from Cooner Wire, Inc. are very flexible and small in diameter (280 um), which let us expect some cable breakage during 11 months of implantation. That did not occur, so we think these wires can be used in future animal trials as long as they are not soldered. The ball-bonding technique applied for connecting the polyimide scaffold of the Hybrid Cuff Electrodes to the adapter substrate appeared to be reliable but could not be investigated sufficiently because of the bad results gained with the solder contacts which inhibited electrical impedance measurements. Plasma-modification of polymer and elastomer surfaces is a powerful tool to improve adhesion. Plasmabonding of silicone bodies is reliable and easy to apply and has probably a great potential with future silicone technologies. Plasma-bonding of polyimide to silicone proved to be extremely reliable in vitro (unpublished) but failed in biological environments. Since this technology is extremely simple to apply and offers a high-yield assembly of delicate polyimide microelectrodes and silicone (which was never achieved using adhesives) further efforts of process optimization will be carried out in future. Conclusion Micromachining of polyimide is a promising technology for realization of small-sized high-channel microelectrodes for investigation of fundamental neural physiology and feasibility of novel neural prosthetic devices. The presented work suggests that an elaborate combination of selected materials (polyimide substrate, titanium/platinum metallization) and technologies (ball-bonding, welding, plasma-treatment) might bring this technology beyond applications for fundamental research. References [1] Ceballos, D., A. Valero-Cabre, E. Valderama, M. Schuettler, T. Stieglitz, and X. Navarro, Morphologic and functional evaluation of peripheral nerve fibers regenerated through polyimide sieve electrodes over long-term implantation. J. Biomed Mater Res., (4): p [2] Schuettler, M. and T. Stieglitz, 18polar hybrid cuff electrodes for stimulation of peripheral nerves. Proc. 5th Annual IFESS Conf., 2000: p [3] Schuettler, M., T. Stieglitz, M. Gross, D. Altpeter, A. Staiger, T. Doerge, and F. Katzenberg, Reducing stiffness and electrical losses in high channel hybrid nerve cuff electrodes. CD-ROM Proc. 23rd Annual IEEE EMBS Conf., 2001.

5 [4] Haberer, W., M. Schuettler, and H.-J. Beutel, Method for producing an electrical and/or mechanical connection between flexible thin-film substrates. Int. Patent No.: WO 02/07486 A1, Acknowledgments: The authors wish to acknowledge the European Community for funding the long-term research projects GRIP (LTR Project No 26322) and Cyberhand (IST Project Reference ). Special thanks go to Prof. X. Navarro (Universitat Autonóma de Barcelona, Spain) and his team for surgery on rats, Prof. P. Rabischong (Université Montpellier I, Montpellier, France) for surgery on goats, and T. Doerge and S. Kammer (Fraunhofer-Institute for Biomedical Engineering, Sankt Ingbert, Germany) for manufacturing of polyimide substrates.