Sarah H. Felix

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

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 ± 9 μm.

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

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.

Insertion of flexible neural probes using rigid stiffeners attached with biodissolvable adhesive.

Microelectrode arrays for neural interface devices that are made of biocompatible thin-film polymer are expected to have extended functional lifetime because the flexible material may minimize adverse tissue response caused by micromotion. However, their flexibility prevents them from being accurately inserted into neural tissue. This article demonstrates a method to temporarily attach a flexible microelectrode probe to a rigid stiffener using biodissolvable polyethylene glycol (PEG) to facilitate precise, surgical insertion of the probe. A unique stiffener design allows for uniform distribution of the PEG adhesive along the length of the probe. Flip-chip bonding, a common tool used in microelectronics packaging, enables accurate and repeatable alignment and attachment of the probe to the stiffener. The probe and stiffener are surgically implanted together, then the PEG is allowed to dissolve so that the stiffener can be extracted leaving the probe in place. Finally, an in vitro test method is used to evaluate stiffener extraction in an agarose gel model of brain tissue. This approach to implantation has proven particularly advantageous for longer flexible probes (>3 mm). It also provides a feasible method to implant dual-sided flexible probes. To date, the technique has been used to obtain various in vivo recording data from the rat cortex.

Optimization of multi-layer metal neural probe design

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.

Improved chronic neural stimulation using high surface area platinum electrodes

We report a novel nano-cluster platinum (NCPt) film that exhibits enhanced performance as an electrode material for neural stimulation applications. Nano-cluster films were deposited using a custom physical vapor deposition process and patterned on a flexible polyimide microelectrode array using semiconductor processing technology. Electrode performance was characterized in vitro using electrochemical impedance spectroscopy and compared with sputtered thinfilm platinum (TFPt) electrodes. We characterized electrode impedance, charge storage capacity, voltage transient properties, and relative surface area enhancement in vitro. Preliminary lifetime testing of the electrode reveals that the NCPt electrodes degrade more slowly than TFPt electrodes. The combination of material biocompatibility, electrochemical performance, and preliminary lifetime results point to a promising new electrode material for neural interface devices.

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

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.

Thin-film, high-density micro-electrocorticographic decoding of a human cortical gyrus

High-density electrocorticography (ECoG) arrays are promising interfaces for high-resolution neural recording from the cortical surface. Commercial options for high-density arrays are limited, and historically tradeoffs must be made between spatial coverage and electrode density. However, thin-film technology is a promising alternative for generating electrode arrays capable of large area coverage and high channel count, with resolution on the order of cortical columns in the functional surface unit of a human gyrus. Here, we evaluate the sensing performance of a high-density thin-film 128-electrode array designed specifically for recording the distributed neural activity of a single human cortical gyrus. We found robust field potential responses throughout the superior temporal gyrus evoked by speech sounds, and clear phonetic feature selectivity at the resolution of 2 mm inter-electrode distance. Decoding accuracy improved with increasing density of electrodes over all three patients tested. Thin-film ECoG has significant potential for high-density neural interface applications at the scale of a human gyrus.

Towards a large-scale recording system: Demonstration of polymer-based penetrating array for chronic neural recording

The brain is a massively interconnected network of specialized circuits. Even primary sensory areas, once thought to support relatively simple, feed-forward processing, are now known to be parts of complex feedback circuits. All brain functions depend on millisecond timescale interactions across these brain networks. Current approaches cannot measure or manipulate such large-scale interactions. Here we demonstrate that polymer-based, penetrating, micro-electrode arrays can provide high quality neural recordings from awake, behaving animals over periods of months. Our results indicate that polymer electrodes are a viable substrate for the development of systems that can record from thousands of channels across months to years. This is our first step towards developing a 1000+ electrode system capable of providing high-quality, long-term neural recordings.

Chronic, percutaneous connector for electrical recording and stimulation with microelectrode arrays.

The translation of advances in neural stimulation and recording research into clinical practice hinges on the ability to perform chronic experiments in awake and behaving animal models. Advances in microelectrode array technology, most notably flexible polymer arrays, have significantly improved reliability of the neural interface. However, electrical connector technology has lagged and is prone to failure from non-biocompatibility, large size, contamination, corrosion, and difficulty of use. We present a novel chronic, percutaneous electrical connector system that is suitable for neural stimulation and recording. This system features biocompatible materials, low connect and disconnect forces, passive alignment, and a protective cap during non-use. We have successfully designed, assembled, and tested in vitro both a 16-channel system and a high density 64-channel system. Custom, polyimide, 16-channel, microelectrode arrays were electrically assembled with the connector system and tested using cyclic voltammetry and electrochemical impedance spectroscopy. This connector system is versatile and can be used with a variety of microelectrode array technologies for chronic studies.

Chronic, multi-contact, neural interface for deep brain stimulation

Recent clinical studies show deep brain stimulation (DBS) as a promising therapy for the chronic treatment of major depression. Although an increasing number of studies have shown the clinical benefits of DBS in patients with major depressive disorder, little is known about the underlying mechanisms by which the treatment works. The neural interface described here consists of two multi-contact, polymer-based, microelectrode arrays that were specially-designed and fabricated. The first is for stimulation of the medial prefrontal cortex (mPFC) and the second is for recording local field potentials (LFPs) and event related potentials (ERPs) in the basolateral amygdala (BLA). Unlike conventional metal wire stimulating arrays, this stimulating array offers 144 spatial configurations, both monopolar and bipolar. We present here preliminary results involving stimulation of various contact points spanning the mPFC, with simultaneous recording from multiple contacts across the temporal lobe.