(K-423) The Effect of Nanopatterned Surfaces on Intracortical Microelectrode Recording Performance

Introduction:: Intracortical microelectrodes record the action potentials from individual neurons. Recordings obtained from microelectrodes can be used to help treat and understand various neurological diseases and disorders. Combining microelectrodes with brain-computer interfaces can restore function for people with paralysis. However, maintaining stable long-term recordings poses a significant challenge. The neuroinflammatory response to microelectrode insertion is likely the primary factor in recording quality over time.

Neurons within the brain live in the extracellular matrix (ECM), which is composed of a fibrous network of proteins. The 200 nanometers diameter protein fibers found in the ECM create a porous and textured microenvironment to facilitate nutrient transport and natural cell migration. The smooth surface of commercially available microelectrodes contrasts the physiological properties of the native ECM. In previous studies, we hypothesized that the physical etching of 200 nm patterned grooves into the surface of planar microelectrodes would facilitate the reduction of the neuroinflammatory response. Our initial work demonstrated reduced neuroinflammatory protein and gene expression for patterned microelectrodes compared to smooth controls. Specifically, we observed a strong correlation between reduced expression of inflammatory-related genes (CD14 and TNF-α), and reduced oxidative stress markers (NOS2), when using nanopatterned electrodes compared to smooth electrodes.

The current study furthers our investigation of the correlation between neuroinflammation and electrode surface architecture, and expands our understanding to the implications in acute recording performance. Here we report on the acute phase of a chronic study of microelectrode recording performance. Once completed, we will also report the post-mortem neuroinflammatory gene expression to characterize neuroinflammation.


Materials and Methods:: Twelve male Sprague Dawley rats were divided into a control group and a nanopatterned electrode group. 16-channel microelectrodes were implanted in the motor cortex. Nanopatterned microelectrodes have etched grooves 200 nm wide, 300 nm apart, and 200 nm deep. All recordings were conducted over 12 weeks, bi-weekly for 10 minutes, when the rat was active.

Data was analyzed to detect single-unit activity and assess MEA performance. Peak-to-peak voltage (Vpp) was defined as the voltage range from peak to trough of each waveform. The noise was calculated as the root-mean-square of the channel after removing spikes. The signal-to-noise ratio (SNR) was calculated by dividing the Vpp of the ensemble unit waveform by the Noise for each unit. Units per channel were calculated by dividing the recording session’s total units by the number of active channels. Recording data from MEA devices that registered multiple active channels were averaged together to determine average values for Vpp, Noise, Noise and the proportion of active electrode channels for single recording sessions.

After 12 weeks, rats will be perfused with PBS followed by 30% sucrose. Brains will be frozen after extraction, sectioned to 150 µm thick, and a 500 µm radius biopsy punch will be centered over the implant site to isolate tissue radial to the implant (~8 punches for a total of 1200 µm depth). Following tissue isolation, samples will be homogenized, and RNA will be extracted to be run on the Nanostring nCounter for gene analysis using a customized panel of 152 neuroinflammatory genes.




Results, Conclusions, and Discussions:: At the current stage of our study, we have successfully concluded the third week of data acquisition, constituting one-fourth of the planned 12-week experimental timeline. . Initially, both types of microelectrodes exhibited comparable percentages of active channels (Figure 1). However, by only three weeks post-implantation, the nanopatterned microelectrodes displaying a progressively higher proportion of active channels compared to the smooth controls. Both electrode types are demonstrating a decline in recording quality, but the control implants show a large decline in the percentage of actively recording channels between weeks two and three.


Our initial findings indicate a correlation between the use of nanopatterned grooves in the microelectrode surface and the reduction in the decline in microelectrode performance, as indicated by the percentage of active channels. Since the study is ongoing, we will include further temporal effects at the conclusion of this study. Based on the trend line, we anticipate that the performance of the nanopatterned microelectrodes will continue to outperform the smooth control device through the duration of out 12-week study.



At the conclusion of the recording study, we will perform RNA extraction from the tissue adjacent the microelectrodes to examine the gene expression patterns of targeted neuroinflammatory genes. The outcome of this study so far holds the promise of providing deeper insights into the neuronal response to implants and will aid in developing improved microelectrode designs aimed at reducing neuroinflammatory response for both basic neuroscience and clinical applications of brain-machine interfaces.




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