An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

Gilgunn, Peter J.; Khilwani, Rakesh; Kozai, Takashi D. Y.; Weber, Douglas J.; Cui, Xinyan Tracy; Erdö́s, G.; Özdoğanlar, O. Burak; Fedder, Gary K.

doi:10.1109/memsys.2012.6170092

Cited by 61 publications

(60 citation statements)

References 8 publications

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“…This decrease in microglial attachment in combination with the decrease in mechanical strain could result in an improved electrode-tissue interface. Indeed, improved tissue responses have been observed with compliant [52–59] and mechanically-adaptive materials [60, 61], and ongoing studies will be used to evaluate our novel soft wires in vivo .…”

Section: Resultsmentioning

confidence: 99%

Elastomeric and soft conducting microwires for implantable neural interfaces

et al. 2015

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Current designs for microelectrodes used for interfacing with the nervous system elicit a characteristic inflammatory response that leads to scar tissue encapsulation, electrical insulation of the electrode from the tissue and ultimately failure. Traditionally, relatively stiff materials like tungsten and silicon are employed which have mechanical properties several orders of magnitude different from neural tissue. This mechanical mismatch is thought to be a major cause of chronic inflammation and degeneration around the device. In an effort to minimize the disparity between neural interface devices and the brain, novel soft electrodes consisting of elastomers and intrinsically conducting polymers were fabricated. The physical, mechanical and electrochemical properties of these materials were extensively characterized to identify the formulations with the optimal combination of parameters including Young’s modulus, elongation at break, ultimate tensile strength, conductivity, impedance and surface charge injection. Our final electrode has a Young’s modulus of 974 kPa which is five orders of magnitude lower than tungsten and significantly lower than other polymer-based neural electrode materials. In vitro cell culture experiments demonstrated the favorable interaction between these soft materials and neurons, astrocytes and microglia, with higher neuronal attachment and a two-fold reduction in inflammatory microglia attachment on soft devices compared to stiff controls. Surface immobilization of neuronal adhesion proteins on these microwires further improved the cellular response. Finally, in vivo electrophysiology demonstrated the functionality of the elastomeric electrodes in recording single unit activity in the rodent visual cortex. The results presented provide initial evidence in support of the use of soft materials in neural interface applications.

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Section: Resultsmentioning

confidence: 99%

Elastomeric and soft conducting microwires for implantable neural interfaces

et al. 2015

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“…These past and emerging studies have motivated the development of compliant or flexible implantable intracortical electrode arrays using polymer substrates such as parylene, polyimide, and polydimethylsiloxane (PDMS) [78–89]. Despite the promise of decreasing the tissue strain local to the implant, compliant polymer electrodes face numerous challenges in practical implementation for chronic intracortical neural recording.…”

Section: Discussionmentioning

confidence: 99%

“…Research and exploration of amorphous (non-crystalline) polymers may be one approach to forming more permanent thermally annealed insulators. Another alternative is to conformally and seamlessly insulate substrates and traces that are floating or suspended (with appropriate sacrificial masks) [89]. In contrast, simple designs such as microwires and bed of needle arrays that are conformally coated with a single layer of polymer insulation may bypasses this polymer-polymer delamination failure.…”

Section: Discussionmentioning

confidence: 99%

Mechanical failure modes of chronically implanted planar silicon-based neural probes for laminar recording

et al. 2015

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Penetrating intracortical electrode arrays that record brain activity longitudinally are powerful tools for basic neuroscience research and emerging clinical applications. However, regardless of the technology used, signals recorded by these electrodes degrade over time. The failure mechanisms of these electrodes are understood to be a complex combination of the biological reactive tissue response and material failure of the device over time. While mechanical mismatch between the brain tissue and implanted neural electrodes have been studied as a source of chronic inflammation and performance degradation, the electrode failure caused by mechanical mismatch between different material properties and different structural components within a device have remained poorly characterized. Using Finite Element Model (FEM) we simulate the mechanical strain on a planar silicon electrode. The results presented here demonstrate that mechanical mismatch between iridium and silicon leads to concentrated strain along the border of the two materials. This strain is further focused on small protrusions such as the electrical traces in planar silicon electrodes. These findings are confirmed with chronic in vivo data (133–189 days) in mice by correlating a combination of single-unit electrophysiology, evoked multi-unit recordings, electrochemical impedance spectroscopy, and scanning electron microscopy from traces and electrode sites with our modeling data. Several modes of mechanical failure of chronically implanted planar silicon electrodes are found that result in degradation and/or loss of recording. These findings highlight the importance of strains and material properties of various subcomponents within an electrode array.

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“…For example, material failure is believed to range from recording site to insulation damages including delamination, crack propagation, hydration which leads to loss of dielectric properties and iconic contamination (Escamilla-Mackert et al, 2009; Gilgunn et al, 2013; Kim et al, 2014; Kozai et al, 2014a; Kozai et al, 2015a; Kozai et al, 2015b; Prasad et al, 2014; Prasad et al, 2012; Sankar et al, 2014; Ware et al, 2014). On the other hand, biological failure modes are believed to be due to the inflammatory reactive tissue response to the implanted electrode (Gilgunn et al, 2012; Jaquins-Gerstl et al, 2011; Karumbaiah et al, 2012; Kozai et al, 2014a; Kozai et al, 2014b; Kozai et al, 2012a; Kozai et al, 2014c; Kozai et al, 2010; Potter et al, 2013; Rennaker et al, 2007; Turner et al, 1999). Unlike material failure modes of implantable electrodes(Kozai et al, 2015b; Prasad et al, 2012; Stensaas and Stensaas, 1978), the mechanism(s) behind the progression of the tissue response and the large variability of observed outcomes are poorly understood (Kozai et al, 2015d).…”

Section: Introductionmentioning

confidence: 99%

Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights

Kozai

Eles

Vazquez

et al. 2016

Journal of Neuroscience Methods

106

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Background Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disease in vivo. While this technique has provided powerful new information, in vivo two-photon chronic imaging around tethered cortical implants, such as microelectrodes or neural probes, present unique challenges. New Method A number of strategies are described to prepare a cranial window to longitudinally observe the impact of neural probes on brain tissue and vasculature for up to 3 months. Results It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting light scattering and preserving window clarity over time. In contrast, low concentration hydrogel sealants failed to prevent cell infiltration and their use at high concentration displaced brain tissue and disrupted probe performance. Comparison with Existing Method(s) The use of silastic sealants allows for a suitable imaging window for long term chronic experiments and revealed new insights regarding the dynamic leukocyte response around implants and the nature of chronic BBB leakage in the sub-dural space. Conclusion The presented method provides a valuable tool for evaluating the chronic inflammatory response and the performance of emerging implantable neural technologies.

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An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

Cited by 61 publications

References 8 publications

Elastomeric and soft conducting microwires for implantable neural interfaces

Elastomeric and soft conducting microwires for implantable neural interfaces

Mechanical failure modes of chronically implanted planar silicon-based neural probes for laminar recording

Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights

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