electrochemical-roughening-thin-film-platinum-macro

Electrochemical Roughening of Thin-Film Platinum Macro and Microelectrodes

This protocol demonstrates a method for electrochemical roughening of thin-film platinum electrodes without preferential dissolution at grain boundaries ...

Lawrence Livermore National Laboratory

Flexible polymer probes are expected to enable extended interaction with neural tissue by minimizing damage from micromotion and reducing inflammatory tissue response. However, their flexibility prevents them from being easily inserted into the tissue. This paper describes an approach for temporarily attaching a silicon stiffener with biodissolvable polyethylene glycol (PEG) so that the stiffener can be released from the probe and extracted shortly after probe placement. A novel stiffener design with wicking channels, along with flip-chip technology, enable accurate alignment of the probe to the stiffener, as well as uniform distribution of the PEG adhesive. Insertion, extraction, and electrode function were tested in both agarose gel and a rat brain. Several geometric and material parameters were tested to minimize probe displacement during stiffener extraction. We demonstrated average probe displacement of 28 Â± 9 Âµm.

Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive.

We present here a microfabrication process for multi-layer metal, multi-site, polymer-based neural probes. The process has been used to generate 1-, 2-, and 4-layer trace metal neural probes with highly uniform and reproducible electrode characteristics. Typically, increasing the number of metal layers is assumed to both reduce the width of the neural probes and minimize the injury and glial scarring caused at the implantation site. We show, however, that increasing the number of trace metal layers does not always result in the minimal probe cross-sectional area. A thorough design analysis reveals that the electrode size, along with other design parameters, have interacting effects on the probe cross-sectional area. Moreover, increasing the trace metal layers in the neural probes also increases the design and fabrication cost/time, as well as the likelihood of probe failure. Consequently, all of these factors must be considered when designing a multi-site, neural probe with the objective of minimizing tissue damage.

Optimization of multi-layer metal neural probe design.

We present here a demonstration of a dual-sided, 4-layer metal, polyimide-based electrode array suitable for neural stimulation and recording. The fabrication process outlined here utilizes simple polymer and metal deposition and etching steps, with no potentially harmful backside etches or long exposures to extremely toxic chemicals. These polyimide-based electrode arrays have been tested to ensure they are fully biocompatible and suitable for long-term implantation; their flexibility minimizes the injury and glial scarring that can occur at the implantation site. The creation of dual-side electrode arrays with more than two layers of trace metal enables the fabrication of neural probes with more electrodes without a significant increase in probe size. This allows for more stimulation/recording sites without inducing additional injury and glial scarring.

Polymer neural interface with dual-sided electrodes for neural stimulation and recording.

We present here a microfabricated, multi-functional neural interface with the ability to selectively apply electrical and chemical stimuli, while simultaneously monitoring both electrical and chemical activity in the brain. Such a comprehensive approach is required to understand and treat neuropsychiatric disorders, such as major depressive disorder (MDD), and to understand the mechanisms underlying treatments, such as pharmaceutical therapies and deep brain stimulation (DBS). The polymer-based, multi-functional neural interface is capable of electrical stimulation and recording, targeted drug delivery, and electrochemical sensing. A variety of different electrode and fluidic channel arrangements are possible with this fabrication process. Preliminary testing has shown the suitability of these neural interfaces for in vivo electrical stimulation and recording, as well as in vitro chemical sensing. Testing of the in vitro drug delivery and combined in vivo functionalities this neural interface are currently underway. 

Microfabricated polymer-based neural interface for electrical stimulation/recording, drug delivery, and chemical sensing--development.

Understanding the detailed dynamics of neuronal networks will require the simultaneous measurement of spike trains from hundreds of neurons (or more). Currently, approaches to extracting spike times and labels from raw data are time consuming, lack standardization, and involve manual intervention, making it difficult to maintain data provenance and assess the quality of scientific results. Here, we describe an automated clustering approach and associated software package that addresses these problems and provides novel cluster quality metrics. We show that our approach has accuracy comparable to or exceeding that achieved using manual or semi-manual techniques with desktop central processing unit (CPU) runtimes faster than acquisition time for up to hundreds of electrodes. Moreover, a single choice of parameters in the algorithm is effective for a variety of electrode geometries and across multiple brain regions. This algorithm has the potential to enable reproducible and automated spike sorting of larger scale recordings than is currently possible.

A Fully Automated Approach to Spike Sorting.

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to years. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site, extracellular recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1,024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track large numbers of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.

High-Density, Long-Lasting, and Multi-region Electrophysiological Recordings Using Polymer Electrode Arrays.

Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip.

Article	Year
Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference\| PubMed ID: 23366031	2012
Optimization of multi-layer metal neural probe design. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference\| PubMed ID: 23367295	2012
Polymer neural interface with dual-sided electrodes for neural stimulation and recording. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference\| PubMed ID: 23367296	2012
Microfabricated polymer-based neural interface for electrical stimulation/recording, drug delivery, and chemical sensing--development. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference\| PubMed ID: 24110897	2013
A Fully Automated Approach to Spike Sorting. Neuron\| PubMed ID: 28910621	2017
High-Density, Long-Lasting, and Multi-region Electrophysiological Recordings Using Polymer Electrode Arrays. Neuron\| PubMed ID: 30502044	2019
A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain. Journal of neural engineering\| PubMed ID: 31216526	2019

Vanessa Tolosa

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