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Implanting mechanics of PEG/DEX coated flexible neural probe: impacts of fabricating methods

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Abstract

Resorbable coatings are processed on flexible implants to facilitate penetrations. However, impacts of fabricating methods on implantation damage of coated probes are unclear. Herein, photosensitive polyimide (PSPI) based flexible neural implants are fabricated through clean-room technology. Polyethyleneglycol (PEG) - dexamethasone (DEX) coatings are processed through an improved micro moulding protocol in micro channels, fabricated by computer-numerical-controlled (CNC) micro milling, laser machining, and deep reactive ion etching (DRIE), respectively. An in vitro testing system is developed, using maximum insertion force \({F}_{max}\) and mean region-of-interest strain \({S}_{mean}\) to accurately evaluate effects of the three fabricating methods on implantation damage at different insertion speed. Rat cerebrum, agarose gel, and silicone rubber are used as brain phantoms for tests. Results show that lower insertion speed, and micro channels fabricated by CNC micro milling or DRIE can minimize implantation damage. The decrease of insertion speed from 2.0 mm/s to 0.5 mm/s reduces \({F}_{max}\) by 76.2% ~85.1% and \({S}_{mean}\) by 11.6% ~14.7%, respectively. Compared with laser machining, CNC micro milling and DRIE ensure dimensional accuracy of the PEG/DEX coating, reducing \({F}_{max}\) by 20.2% ~51.4% and \({S}_{mean}\) by 8.0% ~11.6%, respectively. Compared with biological rat cerebrum, \({F}_{max}\) reduces by 5.8% ~25.1% in agarose gel phantom and increases by 7.7% ~21.0% in silicone rubber phantom, respectively. This study improves processing methods of polymer coatings and reveals mechanical difference between current used abiotic brain phantoms and biological brain tissues. Implantation tests establish quantitative relationship among insertion speed, fabricating methods, and implantation damage.

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References

  • W. Ahuva, Y. James and M. Ellis Flexible, Penetrating Brain Probes Enabled by Advances in Polymer Microfabrication. Micromachines, 7(10) 180 (2016)

  • A. Altuna, E. Bellistri, E. Cid et al., SU-8 based microprobes for simultaneous neural depth recording and drug delivery in the brain Lab on a Chip, 13(7) 1422-1430 (2013)

  • A. Andrei, M. Welkenhuysen, B. Nuttin et al., A response surface model predicting the in vivo insertion behavior of micromachined neural implants. J. Neural. Eng. 9, 016005 (2012)

    Article  Google Scholar 

  • A. Bagolini, S. Ronchin, P. Bellutti et al., Fabrication of Novel MEMS Microgrippers by Deep Reactive Ion Etching With Metal Hard Mask. J. Microelectromech. Syst. 99, 1–9 (2017)

    Google Scholar 

  • J. Barrese, N. Rao, K. Paroo et al., Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates. J. Neural. Eng. 10(6), 066014 (2013)

    Article  Google Scholar 

  • B. Bediz, E. Korkmaz, R. Khilwani et al., Dissolvable Micronedle Arrays for Intradermal Delivery of Biologics: Fabrication and Application. Pharm. Res. 31(1), 117–135 (2014)

    Article  Google Scholar 

  • F. Bowden, D.F. Tabor, The friction and lubrication of solids. Am. J. Phys. 2, 7 (1954)

    MATH  Google Scholar 

  • A. Canales, S. Park, A. Kilias et al., Multifunctional Fibers as Tools for Neuroscience and Neuroengineering. Accounts of Chemical Research 51, 829–838 (2018)

    Article  Google Scholar 

  • F. Ceyssens, M. Welkenhuysen, R. Puers, Anisotropic etching in (3 1 1) Si to fabricate sharp resorbable polymer microneedles carrying neural electrode arrays. J. Micromech. Microeng. 29, 027001 (2019)

    Article  Google Scholar 

  • P. Chan, Q. Li, B. Zhang, et al., In vivo biocompatibility and efficacy of dexamethasone-loaded PLGA-PEG-PLGA thermogel in an alkali-burn induced corneal neovascularization disease model. Eur. J. Pharm. Biopharm. 190-198 (2020)

  • J. Donoghue, Bridging the brain to the world: a perspective on neural interface systems. Neuron 60(3), 511–521 (2008)

    Article  Google Scholar 

  • S. Felix, K. Shah, D. George et al., Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive. Annu. Conf. Proc. IEEE Eng. Med. Biol. Soc. 4 871-874 (2012)

  • C. Foley, N. Nishimura, K. Neeves et al., Flexible microfluidic devices supported by biodegradable insertion scaffolds for convection-enhanced neural drug delivery. Biomed. Microdevices 11(4), 915–924 (2009)

    Article  Google Scholar 

  • L. Griep, F. Wolbers, B. Wagenaar et al., BBB ON CHIP: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed. Microdevices. 15(1), 145–150 (2013)

    Article  Google Scholar 

  • C. Hassler, J. Guy, M. Nietzschmann et al., Intracortical polyimide electrodes with a bioresorbable coating. Biomed. Microdevices. 18(5), 81 (2016)

    Article  Google Scholar 

  • S. Huang, S. Lin, J. Chen, In vitro and in vivo characterization of SU-8 flexible neuroprobe: From mechanical properties to electrophysiological recording. Sens. Actuators. A. Phys. 216, 257–265 (2014)

    Article  Google Scholar 

  • W. Jensen, K. Yoshida, G. Hofmann, In-vivo implant mechanics of flexible, silicon-based ACREO microelectrode arrays in rat cerebral cortex. IEEE Trans. Biomed. Eng. 53(5), 934–940 (2006)

    Article  Google Scholar 

  • A. Johan, T. Fotios, F. Annika et al., An array of highly flexible electrodes with a tailored configuration locked by gelatin during implantation—initial evaluation in cortex cerebri of awake rats. Front. Neurosci. 9, 331 (2015)

    Article  Google Scholar 

  • P. Jolien, A. Rutz, Q. Pascale et al., A bilayered PVA/PLGA-bioresorbable shuttle to improve the implantation of flexible neural probes. J. Neural. Eng. 15, 065001 (2018)

    Article  Google Scholar 

  • Y. Kato, S. Furukawa, S. Kazuyuki et al., Photosensitive-polyimide based method for fabricating various neural electrode architectures. Front. Neuroeng. 5, 11 (2012)

    Article  Google Scholar 

  • D. Kil, M. Carmona, F. Ceyssens et al., Dextran as a Resorbable Coating Material for Flexible Neural Probes. Micromachines 10, 61 (2019)

    Article  Google Scholar 

  • T. Kozai, Z. Gugel, X. Li et al., Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes. Biomaterials 35, 9255–9268 (2014)

    Article  Google Scholar 

  • T. Kozai, A. Jaquins-Gerstl, A. Vazquez et al., Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies. ACS Chem. Neurosci. 6(1), 48–67 (2015)

    Article  Google Scholar 

  • A. Lecomte, V. Castagnola, E. Descamps et al., Silk and PEG as means to stiffen a parylene probe for insertion in the brain: toward a double time-scale tool for local drug delivery. J. Micromech. Microeng. 25, 125003 (2015)

    Article  Google Scholar 

  • A. Lecomte, E. Descamps, C. Bergaud, A review on mechanical considerations for chronically-implanted neural probes. J. Neural. Eng. 15, 031001 (2017)

    Article  Google Scholar 

  • H. Lee, G. Janak, S. Currlin et al., oreign Body Response to Intracortical Microelectrodes Is Not Altered with Dip-Coating of Polyethylene Glycol (PEG). Front. Neurosci. 11, 513 (2017)

    Article  Google Scholar 

  • M. Lo, S. Wang, S. Singh et al., Coating flexible probes with an ultra fast degrading polymer to aid in tissue insertion. Biomed. Microdevices. 17(2), 34 (2015)

    Article  Google Scholar 

  • A. Mercanzini, K. Cheung, D. Buhl et al., Demonstration of cortical recording using novel flexible polymer neural probes. Sens. Act. A. 143, 90–96 (2008)

    Article  Google Scholar 

  • E. Mesa, J. Ramírez, P. Boulanger et al., Inverse-FEM Characterization of a Brain Tissue Phantom to Simulate Compression and Indentation. Ingeniería y Ciencia 8, 16 (2012)

    Google Scholar 

  • J. Ortigoza-iaz, K. Scholten, C. Larson et al., Techniques and Considerations in the Microfabrication of Parylene C Microelectromechanical Systems. Micromachines 9, 422 (2018)

    Article  Google Scholar 

  • J. Pinto, F. Touchard, S. Castagnet et al., DIC Strain Measurements at the Micro-Scale in a Semi-Crystalline Polymer. Exp. Mech. 53(8), 1311–1321 (2013)

    Article  Google Scholar 

  • S. Prakash, S. Kumar, Experimental and theoretical analysis of defocused CO2 laser microchanneling on PMMA for enhanced surface finish. J. Micromech. Microeng. 27, 025003 (2017)

    Article  Google Scholar 

  • S. Rao, R. Chen, A. Larocca, et al Remotely controlled chemomagnetic modulation of targeted neural circuits. Nat. Nanotechnol. 14(10): 1-7 (2019)

  • P. Takmakov, K. Ruda, K. Scott et al., Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species. J. Neural. Eng. 2(2), 026003 (2015)

    Article  Google Scholar 

  • L. Tien, F. Wu, M. Tang-Schomer et al., Silk as a Multifunctional Biomaterial Substrate for Reduced Glial Scarring around Brain-Penetrating Electrodes. Adv. Funct. Mater. 23(25), 3185–3193 (2013)

    Article  Google Scholar 

  • R. Verplancke, M. Cauwe, D. Schaubroeck et al., Development of an active high-density transverse intrafascicular micro-electrode probe. J. Micromech. Microeng. 30, 015010 (2020)

    Article  Google Scholar 

  • F. Wang, X. Cheng, Q. Guo et al., Experimental study on micromilling of thin walls. J. Micromech. Microeng. 29, 015009 (2018)

    Article  Google Scholar 

  • Z. Xiang, S. Yen, N. Xue et al., Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle. J. Micromech. Microeng. 24(6), 065015 (2014)

    Article  Google Scholar 

  • W. Zhang, Y. MaX, Z. Li, Experimental evaluation of neural probe’s insertion induced injury based on digital image correlation method. Med. Phys. 43(1), 505–512 (2016)

    Article  Google Scholar 

  • W. Zhang, J. Tang, Z. Li et al., A novel neural electrode with micro-motion-attenuation capability based on compliant mechanisms—physical design concepts and evaluations. Med. Biol. Eng. Comput. 56(10), 1911–1923 (2018)

    Article  Google Scholar 

  • T. Zhou, G. Hong, T. Fu et al., Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain. PNAS 114(23), 5894 (2017)

    Article  Google Scholar 

Download references

Acknowledgement

The authors thank the financial support from the National Natural Science Foundation of China (Grant No. 51675330). Animal tests in this study were performed according to rules approved by Instrumental Analysis Centre of Shanghai Jiao Tong University.

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  1. School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Wenguang Zhang, Xuhui Zhou, Yuxin He, Liyue Xu & Jie Xie

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  1. Wenguang Zhang
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  2. Xuhui Zhou
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  3. Yuxin He
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Correspondence to Wenguang Zhang.

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Zhang, W., Zhou, X., He, Y. et al. Implanting mechanics of PEG/DEX coated flexible neural probe: impacts of fabricating methods. Biomed Microdevices 23, 17 (2021). https://doi.org/10.1007/s10544-021-00552-5

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