Rapid 3-D Nano-Printing to Create Multi-Thousand-Channel Microelectrode Arrays

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Abstract Recent advances in technology have enabled the sampling of activity from up to a few hundred neurons within a limited area of the brain. These innovations reveal the importance of understanding neural interactions beyond the local, micro-scale – and highlight the current inability to record from sufficient volumes of tissue to understand the meso- and macro-scale computations. We propose to overcome this hurdle, increasing the planar reach and spatial densities of recording sites by using our recently established 3D nanoparticle printing method. The proposed three-dimensional arrays will possess an order of magnitude more recording sites (5000 shanks/cm2 at depths up to 4 mm) at a fraction of the production cost of current technologies. Our proposed design overcomes the field's current limitations of both sampling and structure. Moreover, our technology promises to lead to significant new insights in establishing the meso- and macro- scale circuit dynamics within 3D volumes of tissue. In Aim 1, we will construct the first Massive MicroElectrode Array (MMEA), capable of recording from 5000 channels within a 1 cm2 and up to 4 mm deep volume of tissue (with up to 140 um inter-shank spacing). The resulting shanks will be of variable lengths, spanning 500 to 4000um. These dimensions enable the simultaneous recording of mouse cortical and subcortical structures with minimal tissue damage. The probe shanks we have created are remarkably resilient – bending, but not breaking even under a large displacement and thus tolerating significant misalignment during insertion. Cutting-edge questions also require immense technical flexibility in implementation. Our production method supports the rapid production of different designs using basic AutoCAD software. This feature enables the on-demand, study-specific prototyping of new electrode configurations in a few hours. In Aim 2, we will validate and refine in vivo probe performance. The long-term goal of this product is to produce an essential, yet inexpensive neurophysiology tool. We will establish the probe's functionality and maximize the quality of the signals obtained from individual neurons in vivo in the mouse. As a first step, we will monitor neural activity while a head fixed animal walks on a treadmill. Through comparison with silicon probe recordings already obtained, this step will validate the quality of signal from different depths within individual brain areas. Next, we will optogenetically evoke neural activity from neural sub-populations. Direct somatic stimulation will provide a causal measure of the responsiveness of the probe and determine its photoelectric sensitivity.