Abstract
Neural recordings made to date through various approaches—both in-vitro or in-vivo—lack high spatial resolution and a high signal-to-noise ratio (SNR) required for detailed understanding of brain function, synaptic plasticity, and dysfunction. These shortcomings in turn deter the ability to further design diagnostic, therapeutic strategies and the fabrication of neuro-modulatory devices with various feedback loop systems. We report here on the simulation and fabrication of fully configurable neural micro-electrodes that can be used for both in vitro and in vivo applications, with three-dimensional semi-insulated structures patterned onto custom, fine-pitch, high density arrays. These microelectrodes were interfaced with isolated brain slices as well as implanted in brains of freely behaving rats to demonstrate their ability to maintain a high SNR. Moreover, the electrodes enabled the detection of epileptiform events and high frequency oscillations in an epilepsy model thus offering a diagnostic potential for neurological disorders such as epilepsy. These microelectrodes provide unique opportunities to study brain activity under normal and various pathological conditions, both in-vivo and in in-vitro, thus furthering the ability to develop drug screening and neuromodulation systems that could accurately record and map the activity of large neural networks over an extended time period.
Highlights
Neural recordings made to date through various approaches—both in-vitro or in-vivo—lack high spatial resolution and a high signal-to-noise ratio (SNR) required for detailed understanding of brain function, synaptic plasticity, and dysfunction
In an attempt to fill these gaps, microelectrodes embedded in Multi-Electrode Arrays (MEAs) are routinely interfaced with a variety of homogeneous cell culture and brain slice preparations maintained in-vitro[4,5,6,7]
While MEAs are useful in their utility to monitor neural activity simultaneously at multiple sites, this approach is limited in its spatio-temporal resolution[8,9], even more so when tentatively interfaced with brain slices
Summary
Neural recordings made to date through various approaches—both in-vitro or in-vivo—lack high spatial resolution and a high signal-to-noise ratio (SNR) required for detailed understanding of brain function, synaptic plasticity, and dysfunction. These limitations are due mainly to three factors: (1) traditional planar electrodes used in MEAs only record neural activity from the outer and “traumatized” layers of brain slices, which harbour a larger population of either dead or dying cells[4]; (2) the surface of the tissue damaged during slicing often releases proteases and ions, such as potassium and sodium, which in turn result in excitotoxicity of the adjacent area, causing further tissue damage at the recording site resulting in electrical artefacts; (3) the perfusion system required to provide a continuous flow of nutrients and oxygen at a set temperature to maintain the brain slice creates a flow of charged ions within the recording chamber and around the microelectrodes, generating electrical noise[11,12] (Fig. 1a). Unlike most previously published work on microelectrodes, the fabrication process presented here is scalable and adaptable for clinical monitoring and therapeutic applications such as intracranial monitoring and brain machine interfaces
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