Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings

Sara Pimenta,João Gaspar,Patricia Monteiro,José A Rodrigues,Francisca Machado,João F Ribeiro,Oleksandr Bondarchuk,Luis Jacinto,José H Correia,Marino J Maciel

doi:10.3389/fnins.2021.663174

Sara Pimenta, João Gaspar + Show 8 more

Open Access

https://doi.org/10.3389/fnins.2021.663174

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Abstract

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 μm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 μm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes’ mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.

Highlights

Silicon-based neural probes have taken the stage of neuronal recordings over the last decade, especially for acute applications
The electrode sites, vias and contact pads of the top layer were defined by UV photolithography with direct laser writing laser (DLW) and photoresist (AZ P4110 from MicroChemicals), and patterned by reactive ion etching (RIE), followed by O2 stripping to remove the remaining photoresist (Figures 1H,I)
The use of non-photodefinable polyimide permitted the implementation of low-cost etching fabrication procedures

Summary

Introduction

Silicon-based neural probes have taken the stage of neuronal recordings over the last decade, especially for acute applications. These probes can be fabricated through highly reproducible procedures, support many conductive electrodes and exhibit great stability (Buzsáki et al, 2015; Jun et al, 2017b; Ulyanova et al, 2019). Flexible neural probes can be highly conformable, providing adaption to brain micro- and macro-motions (Moshayedi et al, 2014; Spencer et al, 2017) by reducing tissue. Several flexible neural probes based on polymer substrates such as polyimide, SU-8 or Parylene C has been recently proposed with various designs (Weltman et al, 2016; Fan et al, 2020)

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