Available online at ScienceDirect. Procedia Engineering 168 (2016 ) th Eurosensors Conference, EUROSENSORS 2016

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1 Available online at ScienceDirect Procedia Engineering 168 (2016 ) th Eurosensors Conference, EUROSENSORS 2016 A foldable neural electrode for 3D stimulation of deep brain cavities Dries Kil a, *, Philippe De Vloo b, Bart Nuttin b, Robert Puers a a KU Leuven dept. ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Leuven, Belgium b KU Leuven research group Experimental Neurosurgery and Neuranatomy, O&N 1 Herestraat 49, 3000 Leuven, Belgium Abstract In this work a new type of foldable neural electrode is presented. The microfabricated electrode is specifically designed for Deep Brain Stimulation of the cavity wall of thalamic lesions resulting from brain infarcts. On implantation, the electrode is introduced through a cannula, after which the flower-like structure unfolds, contacting the cavity walls and allowing stimulation at different anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching (RIE) is presented. In-Vivo experiments have also been performed in which the implantation procedure and the unfolding of the electrode are tested and visualized The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license 2016 The Authors. Published by Elsevier Ltd. ( Peer-review under responsibility of the organizing committee of the 30th Eurosensors Conference. Peer-review under responsibility of the organizing committee of the 30th Eurosensors Conference Keywords: Neural electrode, thalamic lesion, 3D stimulation, BCI, BMI, neural stimulation, thin film, microfabrication 1. Introduction The human brain can contain cavities due to cell loss caused by e.g. developmental effects, strokes or tumor resection. Since the involved neural networks can no longer function properly, these cavities are often accompanied by various symptoms such as chronic pain or reduced motor function [1]. Although there are different treatment options such as medication [2] or Deep Brain Stimulation (DBS) of the affected regions of the brain [3], these methods are only effective for a limited number of medical conditions. A novel approach is hypothesized where the aforementioned clinical symptoms can potentially be alleviated by direct stimulation of the cavity wall. * Corresponding author. Tel.: ; fax: +32-(0) address: dries.kil@esat.kuleuven.be The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( Peer-review under responsibility of the organizing committee of the 30th Eurosensors Conference doi: /j.proeng

2 138 Dries Kil et al. / Procedia Engineering 168 ( 2016 ) In this paper we describe the design and fabrication of a foldable microelectrode which contains multiple stimulation sites and can be implanted subcortically. This allows stimulation at various anatomical locations on the inner cavity wall, compared to conventional DBS electrodes where multiple micro-electrodes need to be implanted for this purpose. As the cavities are located at a certain depth inside the brain a custom implantation procedure is developed as well. The validity of the designed electrode is tested in a rat model. To test the hypothesis, a specific clinical condition associated with brain cavities was chosen, namely Central Post-Stroke Pain (CPSP). CPSP is a neuropathic pain syndrome that can occur after an ischemic or hemorrhagic stroke, typically located in the sensory thalamus. It is characterized by pain and sensory abnormalities in the body parts corresponding to the affected brain region. [4] 2. Electrode design and implantation procedure The microelectrode is a custom design based on the specifics of the aforementioned clinical condition. The stimulation target is a cavity located in the sensory thalamus, which is situated at a depth of approximately 3 mm (relative to the dura mater). The cavity has a diameter of roughly 2 mm. An implantation procedure is developed as well in order to minimize the damage to the healthy tissue surrounding the implantation trajectory. The above requirements were achieved by designing a highly flexible thin film electrode with a flower-like shape. The device features a 40 mm long lead and a flower-shaped electrode tip containing 7 platinum electrodes with a surface area of mm2. The platinum conductors are isolated between 2 layers of 7 m thick polyimide (PI). The diameter of the electrode-tip (Fig. 1) can be optimized with regard to the size of the target cavity. Based on the MRI-scans (Fig. 5) of our rat model (post-lesioning) a diameter of 3 mm was chosen. The device is fabricated using a MEMS-compatible fabrication process, allowing high volume production with a high turnover rate. Prior to implantation, the electrode is inserted into a cannula (inner diameter: 800 m) using a thin titanium stylet with a diameter of 600 m. When a force is applied to the center of the flower-like structure (Fig. 1) the electrode folds onto itself as it is pushed through the cannula. The assembled device (Fig. 3) is then implanted into the brain using a stereotactic frame. Once in the right position, the electrode is pushed through the cannula using the titanium stylet. The thin PI bridging structures that connect the electrode-contacts force the electrode to unfold, creating contact with the cavity wall. Fig. 1. Flower shaped electrode tip. Fig. 2. Connector, electrode (bottom), stylet and PEEK cannula (top). Fig. 3. Close-up view of the assembled device, ready for implantation.

3 Dries Kil et al. / Procedia Engineering 168 ( 2016 ) Materials Polyimide is chosen as the base material for the device because of its dielectric properties, mechanical flexibility and biocompatibility as described by B. Rubehn et al. [5]. PI is stable in a physiological environment and is non-toxic to the surrounding cells. The flexibility of PI significantly increases the mechanical compliance between the device and the soft biological tissue surrounding it. This prevents micromotions which often lead to inflammation and glial scarring. 4. Fabrication process The devices were made using a two-mask, three-layer lithographic process which is described below.

4 140 Dries Kil et al. / Procedia Engineering 168 ( 2016 ) (1) 4 silicon substrate (7) Lift-off (2) Sacrificial SiO 2 deposition (8) PI-2611 spin-coating (7 µm) (3) PI-2611 spin-coating (7 µm) (9) Metal mask deposition (Al) (4) Photoresist spin-coating (LOR10B / S1818) (10) Reactive Ion Etching of PI (5) Photoresist exposure and development (6) Pt sputtering (400 nm) Fig. 4. Electrode fabrication process. (11) Oxide strip in HF The microfabrication of the electrode is done on a 4 inch Si wafer substrate. A 400 nm thick sacrificial SiOx layer is grown on the substrate by wet thermal oxidation. In a second step a 7 µm thick PI layer (HD microsystems PI 2611) is spin-coated on top of the oxide layer. This first layer of PI is cured at 205 C (opposed to the 340 C proposed by the manufacturer) to create a layer with a higher reactivity to the second PI layer which is deposited in a later step. This improves the lifetime of the device with a factor of 7.5 as was proven by F. Ceyssens et al. [6] The 400 nm thick Pt conductors are deposited by sputter coating and patterned using a lift-off method based on a double layer of LOR10B and S1818 photoresist with a subsequent release step in NMP (n-methyl-2- pyrrolidone) at room temperature. Afterwards a second layer of PI is deposited and fully cured at 340 C. The structures are then patterned by Reactive Ion Etching (RIE) using an aluminium hard mask. In a final step the wafer is soaked in a 5% HF solution which removes the Al hard mask and underetches the sacrificial SiOx layer. After 1 hour of etching the adhesion between the PI electrode and the carrier wafer is reduced and the electrodes can be peeled off using tweezers.

5 Dries Kil et al. / Procedia Engineering 168 ( 2016 ) In vivo experiment To assess if the designed electrode lives up to the requirements, an in vivo experiment is carried out on a rat model. Thalamic lesions are created electrolytically and visualized using Magnetic Resonance Imaging (MRI). After the size and location of the cavity is determined the electrode is implanted using the aforementioned procedure. To make sure that the electrodes are implanted correctly and unfold as expected, a CT-scan is taken to visualize the platinum conductors of the electrode. The conductors are purposely sputtered quite thick (400 nm) so they can be Fig. 5. MRI-scan (axial plane). Fig. 6. CT-scan (axial plane). Fig. 7. Post-surgery image showing the implanted electrode. easily visualized on the aforementioned scan. The MRI-scan clearly shows the presence of the created cavity in the brain of the rat. As can be deduced from Fig. 5 the cavity has a diameter of approximately 2 mm. The post-implantation CT-scan (Fig. 6) shows that the interelectrode distance is approximately 2 mm, which coincides with the calculated diameter of the cavity. This confirms that the electrode unfolded correctly and is in close contact with the side walls. 6. Conclusion We demonstrated the design and fabrication of a foldable microelectrode suitable for 3D stimulation of deep brain cavities using microfabrication tools. An in-vivo experiment confirmed that the electrode unfolds correctly and can be used for future stimulation experiments. Acknowledgements The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/ ) / ERC grant agreement n , and the KU Leuven IDO program, project on electrical brain stimulation IDO/12/024. References [1] G. Schott, From thalamic syndrome to central poststroke pain, J. Neurol. Neurosurg. Psychiatry 61 (1996), [2] J Kalita, A Vajpayee, Comparison of rednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. QJM 99 (2006), [3] A.C. Sutton et al., Deep brain stimulation of the substantia nigra pars reticulata improves forelimb akinesia in the hemiparkinsonian rat. J. Neurophysiol. 109 (2013), [4] H. Klit, N.B. Finnerup, T.S. Jensen, Central post-stroke pain: clinical characteristics, pathophysiology, and management, Lancet Neurol. 9 (2009),

6 142 Dries Kil et al. / Procedia Engineering 168 ( 2016 ) [5] B. Rubehn, T. Stieglitz, In vitro evaluation of the long-term stability of polyimide as a material for neural implants, Biomaterials 31 (2010), [6] F. Ceyssens, B. Puers, Insulation lifetime improvement of polyimide thin film neural implants. J. Neural. Eng. (2015) 12,