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

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.

Integrated Micro-Devices for a Lab-in-Organoid Technology Platform: Current Status and Future Perspectives

“…Solutions previously developed in our lab (see Angotzi et al, 2019a ; Lecomte et al, 2020 ; Ribeiro et al, 2021 ) for post-processing CMOS dies and (bio)materials functionalization can be adapted for extracting single μRadios from the bulky silicon either from single dies or from whole CMOS wafers. Furthermore, using author’s previous experience with polyimide based neural interfaces ( Simi et al, 2014 ; Rodrigues et al, 2020 ; Pimenta et al, 2021 ), polyimide-based 3D structures with through polymer vias ( Hussain and Hussain, 2016 ) can be used to integrate the designed antenna between polyimide layers, routing the electrodes to the top surface of the micro-device ensuring the biocompatibility.…”

From End to End: Gaining, Sorting, and Employing High-Density Neural Single Unit Recordings

“…As the time span of recorded data is increasingly substantial, it is recommended that beginning with polytrodes, data should be split into subsets, in a divide-and-conquer fashion (Swindale and Spacek, 2014 ; Lee et al, 2017 ; Diggelmann et al, 2018 ). Besides the probes by Plexon described above, there have been endeavors to upscale channel count mainly by placing electrodes as close as possible, thus keeping physical expansion of the channel ensembles at the bottom (Pimenta et al, 2021 ; Steinmetz et al, 2021 ; Wang et al, 2021 ). The rationale behind spatial oversampling or spacing recording sites so tightly that SUAs and background activity are clearly separable is not only to boost recording quality and neuron discriminability (Diggelmann et al, 2018 ) but to assess the accuracy of a newly engineered spike sorting algorithm without knowing the ground truth data (Zhang and Constandinou, 2021a ).…”

Parylene C as an Insulating Polymer for Implantable Neural Interfaces: Acute Electrochemical Impedance Behaviors in Saline and Pig Brain In Vitro

“…Characterization of neural electrodes can be conducted in various electrolyte models, such as normal saline [ 11 , 12 , 13 , 14 ], phosphate-buffered saline (PBS) [ 15 , 16 , 17 ] and interstitial fluid (ISF) [ 18 , 19 ], as well as neural tissue in vivo. Meanwhile, the performance of Parylene as an insulating polymer has been studied in these regular electrolyte solutions and in vivo [ 20 , 21 ].…”