000865223 001__ 865223
000865223 005__ 20240619091252.0
000865223 0247_ $$2doi$$a10.3389/conf.fncel.2018.38.00072
000865223 037__ $$aFZJ-2019-04757
000865223 082__ $$a610
000865223 1001_ $$0P:(DE-Juel1)165188$$aRincón Montes, Viviana$$b0$$eCorresponding author
000865223 1112_ $$a11th Int. Meeting on Substrate Integrated Microelectrode Arrays$$cReutlingen$$d2018-07-04 - 2018-07-06$$gMEA Meeting 2018$$wGermany
000865223 245__ $$aFrom stiff silicon to compliant retinal and cortical multisite penetrating implants
000865223 260__ $$aLausanne$$bFrontiers Research Foundation$$c2018
000865223 300__ $$a0
000865223 3367_ $$2ORCID$$aCONFERENCE_PAPER
000865223 3367_ $$033$$2EndNote$$aConference Paper
000865223 3367_ $$2BibTeX$$aINPROCEEDINGS
000865223 3367_ $$2DRIVER$$aconferenceObject
000865223 3367_ $$2DataCite$$aOutput Types/Conference Paper
000865223 3367_ $$0PUB:(DE-HGF)8$$2PUB:(DE-HGF)$$aContribution to a conference proceedings$$bcontrib$$mcontrib$$s1568813683_18880
000865223 520__ $$aMotivation: 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.
000865223 536__ $$0G:(DE-HGF)POF3-552$$a552 - Engineering Cell Function (POF3-552)$$cPOF3-552$$fPOF III$$x0
000865223 588__ $$aDataset connected to CrossRef
000865223 7001_ $$0P:(DE-Juel1)169539$$aSrikantharajah, Kagithiri$$b1
000865223 7001_ $$0P:(DE-Juel1)159559$$aKireev, Dmitry$$b2
000865223 7001_ $$0P:(DE-Juel1)174123$$aLange, Jaqueline$$b3
000865223 7001_ $$0P:(DE-Juel1)128713$$aOffenhäusser, Andreas$$b4
000865223 773__ $$0PERI:(DE-600)2452963-1$$a10.3389/conf.fncel.2018.38.00072$$gVol. 12$$v12$$x1662-5102$$y2018
000865223 909CO $$ooai:juser.fz-juelich.de:865223$$pVDB
000865223 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFRONT CELL NEUROSCI : 2017
000865223 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000865223 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000865223 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000865223 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central
000865223 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000865223 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000865223 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000865223 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000865223 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000865223 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000865223 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)165188$$aForschungszentrum Jülich$$b0$$kFZJ
000865223 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)169539$$aForschungszentrum Jülich$$b1$$kFZJ
000865223 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)159559$$aForschungszentrum Jülich$$b2$$kFZJ
000865223 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)174123$$aForschungszentrum Jülich$$b3$$kFZJ
000865223 9101_ $$0I:(DE-HGF)0$$6P:(DE-Juel1)174123$$aICS-8$$b3
000865223 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)128713$$aForschungszentrum Jülich$$b4$$kFZJ
000865223 9131_ $$0G:(DE-HGF)POF3-552$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vEngineering Cell Function$$x0
000865223 9141_ $$y2019
000865223 920__ $$lyes
000865223 9201_ $$0I:(DE-Juel1)ICS-8-20110106$$kICS-8$$lBioelektronik$$x0
000865223 980__ $$acontrib
000865223 980__ $$aVDB
000865223 980__ $$aI:(DE-Juel1)ICS-8-20110106
000865223 980__ $$aUNRESTRICTED
000865223 981__ $$aI:(DE-Juel1)IBI-3-20200312