From stiff silicon to compliant retinal and cortical multisite penetrating implants

• ¹ Forschungszentrum Jülich, Institute of Complex Systems 8 (Bioelectronics), Germany

Motivation: For years, silicon has been successfully used as the standard substrate material for the fabrication of penetrating neural probes that perform electrical recording as well as stimulation of single or multiple neuronal cells in vivo. Nevertheless, the mechanical mismatch between the stiff silicon and the surrounding soft tissue enhances acute inflammatory responses [1] and hampers the long-term stability and performance of such implants due to glial scarring as a consequence of foreign body responses [2]. With the aim to fabricate more compliant neural probes, the flexibility and softness of different polymer materials are considered in this work for the optimization of the design and fabrication of compliant retinal and cortical multisite penetrating microelectrode arrays (MEAs). Furthermore, the insertion of the proposed flexible systems is assessed theoretically and tested experimentally for both retina and brain tissues. In this work, we show the possibility to perform electrical recording and stimulation with multisite penetrating MEAs from both: thick brain tissue and thin retina. Materials and Methods: Flexible substrate materials, such as polyimide (Pi), parylene-C (Pa-C), and polydimethylsiloxane (PDMS) are used for the fabrication of compliant neural probes. The thickness (3-10 µm), the width (50-100 µm), and the length (140-1000 µm) of a multi-shank design were optimized in order to increase the theoretical buckling force threshold for short/medium and long penetrating shanks. Flexible structures with the aforementioned thicknesses are compared with Si-based structures through insertion tests in phantom neural tissues, which are made out of PDMS mixed at different polymer/curing agent ratios to achieve a Young’s modulus akin to brain and retina (10kPa and 23kPa respectively). Following the established designs, photolithography and reactive-ion etching (RIE) techniques are used for the microfabrication of such flexible devices. In addition, to further increase the flexibility of the compliant probes, conductive polymers and stretchable conductive layers with serpentine and mesh designs are tested. Furthermore, the feasibility to perform electrical recording and stimulation is first tested with silicon based probes in light-adapted wildtype retina in vitro. Results: Optimization of cross-sectional dimensions show a higher buckling force threshold for lower aspect ratio designs (e.g. 140 µm long and 100 µm wide). Likewise, the calculation of buckling force threshold for the different materials show that a thickness of 6-10 µm should withstand the insertion of silicon, Pi, and Pa-C probes when applying a tethering force of 1mN, as is the case for brain tissue [1, 2]. In contrast, PDMS would require a minimal thickness of approximately 70 µm. The theoretical calculations are also confirmed experimentally with the probes penetration into phantom and real tissue. Moreover, the use of penetrating MEAs and recording inside the thin retinal tissue is proved to be feasible. Discussion and Conclusion: The development of penetrating and at the same time compliant neural probes requires a trade-off between design considerations (length, width, and thickness) and the mechanical properties of the materials to be used during fabrication. On one hand, flexible materials in an optimized cross-sectional design might be used, however these are constrained to the necessary length and maximum accepted thickness of the implant to fulfill the requirements of the target application. For example, while retinal applications demand short shafts, long ones are required for brain. On the other hand, the use of soft materials like PDMS is limited in their use because their high softness drags out its handling during fabrication and usage. Although an increase in thickness might overcome some processing difficulties, the required thickness for it might generate even higher trauma than when using a stiff material, since a higher amount of tissue is displaced during insertion. Hence, when working with flexible and ultrathin implants, a proper strategy to insert such systems into the tissue must be developed. Even though different stiff and biodegradable shuttle solutions have been proposed in the literature [1, 2], wafer scale processes compatible with MEMS technology are still a challenge. Therefore, in this work, further fabrication steps comprising the integration of dry patterning and lift-off techniques, as well as micro-molding, and bio-degradable polymers are investigated for the development of neural probes with built-in insertion shuttles.